LSM1

UniProt ID: P47017
Organism: Saccharomyces cerevisiae
Review Status: COMPLETE
Aliases:
SPB8 YJL124C J0714
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Gene Description

LSM1 (Lsm1p) is the defining component of the cytoplasmic Lsm1-7-Pat1 heptameric complex, which is a critical activator of mRNA decapping and a key effector of deadenylation-dependent mRNA decay. Unlike other Lsm proteins (Lsm2-8) that function in U6 snRNA splicing, LSM1 is unique and forms a complex specifically involved in cytoplasmic mRNA turnover. The Lsm1-7 complex binds to poly(U) tracts at the 3' end of deadenylated mRNAs and recruits the decapping machinery (Dcp1/Dcp2), converting capped mRNAs to susceptible substrates for 5' to 3' exonucleolytic degradation by Xrn1. The complex also functions in protective binding to mRNA 3' ends. LSM1 is predominantly cytoplasmic but can also localize to P-bodies and has been detected in the nucleus.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0000290 deadenylation-dependent decapping of nuclear-transcribed mRNA
IBA
GO_REF:0000033 		ACCEPT
Summary: Phylogenetic annotation indicating that LSM1 is involved in deadenylation-dependent decapping of nuclear-transcribed mRNA based on ortholog inference. This annotation is well-supported by experimental evidence from multiple sources, including IMP annotations with PMIDs 10761922 and 15716506, which directly demonstrate the role of Lsm1p in mRNA decapping.
Reason: This is a core function of LSM1. The annotation is correct and represents the primary mechanistic role of the Lsm1-7-Pat1 complex. Bouveret et al. (2000) demonstrated that Lsm1p-Lsm7p complex activates the decapping step of mRNA degradation, with deletion mutants showing accumulation of capped mRNAs and blocks in mRNA decay. This is a conserved function across eukaryotes and LSM1 is the defining member of this pathway.
Supporting Evidence:
PMID:10747033
Deletions of LSM1, 6, 7 and PAT1 genes increased the half-life of reporter mRNAs. Interestingly, accumulating mRNAs were capped, suggesting a block in mRNA decay at the decapping step.
PMID:10761922
mutations in seven yeast Lsm proteins (Lsm1-Lsm7) also lead to inhibition of mRNA decapping
PMID:15716506
The decapping of eukaryotic mRNAs is a key step in their degradation. The heteroheptameric Lsm1p-7p complex is a general activator of decapping
file:yeast/LSM1/LSM1-deep-research-falcon.md
The Lsm1-7 ring plus Pat1 is a key module that links 3' end status to decapping: Pat1/Lsm1-7 binds oligoadenylated 3' ends and helps recruit/activate the decapping enzyme.
GO:0003729 mRNA binding
IBA
GO_REF:0000033 		ACCEPT
Summary: Phylogenetic inference of mRNA binding capacity. This is mechanistically accurate as the Lsm1-7 complex binds to oligo-U tracts at the 3' end of deadenylated mRNAs, which is essential for its decapping activation function. The annotation is supported by IDA evidence (PMID:23222640) that demonstrates LSM1 association with yeast mRNPs.
Reason: LSM1 is a core component of the Lsm1-7 complex that binds to poly(U) tracts of mRNA 3' ends as part of its mechanism for mRNA decay activation. The mRNA binding is functionally relevant to the decapping activation role. The complex specifically recognizes RNA motifs via the ring-structured Sm domain.
Supporting Evidence:
PMID:15716506
Mutations affecting the predicted RNA-binding and inter-subunit interaction residues of Lsm1p led to impairment of mRNA decay, suggesting that the integrity of the Lsm1p-7p complex and the ability of the Lsm1p-7p complex to interact with mRNA are important for mRNA decay function
PMID:24139796
The 3.7 Γ… resolution structure of Lsm1-7 bound to the C-terminal domain of Pat1 reveals...A distinct structural feature of the cytoplasmic Lsm ring is the C-terminal extension of Lsm1, which plugs the exit site of the central channel and approaches the RNA binding pockets.
GO:1990726 Lsm1-7-Pat1 complex
IBA
GO_REF:0000033 		ACCEPT
Summary: Phylogenetic annotation indicating LSM1 is a component of the Lsm1-7-Pat1 complex. This is well-supported by IDA evidence (PMID:24139796) that provides crystal structure of the complex, confirming LSM1 as a core subunit.
Reason: LSM1 is the defining member of the Lsm1-7-Pat1 complex, forming the heptameric ring that recruits Pat1 for mRNA decay activation. Sharif & Conti (2013) resolved the 2.3 Γ…ngstrΓΆm crystal structure showing Lsm1-2-3-6-5-7-4 topology with LSM1 as the unique subunit. This is factual component annotation.
Supporting Evidence:
PMID:10747033
Lsm1p, together with Lsm2p-Lsm7p, forms a new seven-subunit complex...the Lsm1p-Lsm7p complex is associated with Pat1p and Xrn1p exoribonuclease
PMID:24139796
The 2.3 Γ… resolution structure of S. cerevisiae Lsm1-7 shows the presence of a heptameric ring with Lsm1-2-3-6-5-7-4 topology
GO:0000932 P-body
IBA
GO_REF:0000033 		ACCEPT
Summary: Phylogenetic inference that LSM1 is active in or localized to P-bodies. This is accurate as Lsm1-7 is a core component of P-bodies where mRNA decapping and decay occur. Multiple IDA and IMP annotations (PMIDs 12730603, 18611963) directly support localization and function in P-bodies.
Reason: LSM1 and the Lsm1-7-Pat1 complex are core P-body components. Sheth & Parker (2003) demonstrated that proteins involved in mRNA decapping are concentrated in P-bodies, and that mRNA degradation intermediates localize to these structures. The complex is active_in P-bodies as the primary site of its mRNA decay function.
Supporting Evidence:
PMID:12730603
proteins that activate or catalyze decapping are concentrated in P bodies...mRNA degradation intermediates are localized to P bodies
GO:0000932 P-body
IEA
GO_REF:0000044 		ACCEPT
Summary: UniProt subcellular location mapping indicates P-body localization based on automated annotation. This is consistent with experimental evidence but is weaker than IBA inference or direct experimental evidence.
Reason: P-body localization is correct and well-supported. While this IEA annotation is lower confidence than the IBA and IDA annotations, it is not incorrect and represents the same underlying biological reality. All annotations for P-body are consistent across different evidence types, confirming LSM1 localization to this critical mRNA decay compartment.
GO:0000956 nuclear-transcribed mRNA catabolic process
IEA
GO_REF:0000002 		KEEP AS NON CORE
Summary: This parent mRNA catabolic process term is valid but broader than the specific decay subprocesses curated for LSM1.
Reason: Changed from MODIFY to KEEP_AS_NON_CORE because the review rationale supports retaining the broad parent term as non-core rather than replacing it.
GO:0003723 RNA binding
IEA
GO_REF:0000120 		KEEP AS NON CORE
Summary: IEA annotation based on InterPro Sm domain and RNA-binding keywords. While LSM1 does bind RNA via its Sm domain, this is a generic parent term that is superseded by GO:0003729 (mRNA binding) which is more specific.
Reason: GO:0003723 (RNA binding) is technically correct but overly general compared to GO:0003729 (mRNA binding), which specifies the actual substrate and mechanism. LSM1 specifically binds mRNA (particularly poly(U) tracts) rather than other RNA types like snRNAs. The more specific mRNA binding term is already present with IBA and IDA evidence. This general RNA binding term is redundant and less informative.
GO:0005634 nucleus
IEA
GO_REF:0000044 		ACCEPT
Summary: UniProt subcellular location mapping to nucleus. LSM1 has been detected in the nucleus according to the UniProt record, and there is IDA evidence (PMID:23706738) supporting nuclear localization.
Reason: LSM1 is present in both nucleus and cytoplasm. The UniProt entry states nuclear localization with ECO:0000269|PubMed:10761922 evidence. While the primary function of LSM1 is in the cytoplasm for mRNA decay, nuclear detection is documented and the annotation is correct.
Supporting Evidence:
PMID:10761922
the Lsm1-Lsm7 proteins co-immunoprecipitate with the mRNA decapping enzyme (Dcp1), a decapping activator (Pat1/Mrt1) and with mRNA
GO:0005737 cytoplasm
IEA
GO_REF:0000120 		ACCEPT
Summary: IEA annotation indicating cytoplasmic localization based on automated inference. This is correct and reflects the primary location of LSM1 where the mRNA decay machinery operates.
Reason: LSM1 is predominantly localized to the cytoplasm where it functions in mRNA decay and P-body assembly. This is well-documented by multiple IDA annotations and is essential to its biological function.
GO:0006397 mRNA processing
IEA
GO_REF:0000043 		REMOVE
Summary: UniProt keyword mapping indicates LSM1 involvement in mRNA processing. However, this is misleading because mRNA processing typically refers to 5' capping, 3' polyadenylation, and splicing of nascent transcripts.
Reason: This annotation is mechanistically incorrect for LSM1. GO:0006397 (mRNA processing) encompasses 5' capping, 3' polyadenylation, and splicing during transcription. LSM1 functions in mRNA decay/degradation, not mRNA processing. The Lsm1-7 complex removes the 5' cap as part of decay, but this is degradation, not processing. The specific mRNA decay processes (GO:0000288, GO:0000290) are the correct annotations. This IEA annotation appears to result from incorrect keyword mapping and should not be retained.
GO:0032991 protein-containing complex
IEA
GO_REF:0000117 		ACCEPT
Summary: ARBA machine learning annotation indicating LSM1 is part of a protein-containing complex. This is correct as LSM1 is a core member of the Lsm1-7-Pat1 complex.
Reason: LSM1 is an obligate component of the heptameric Lsm1-7-Pat1 complex. This is a generic parent term but accurate. More specific component annotations exist (GO:1990726 for the specific complex).
GO:1990904 ribonucleoprotein complex
IEA
GO_REF:0000043 		ACCEPT
Summary: UniProt keyword mapping indicates LSM1 is part of a ribonucleoprotein complex. The Lsm1-7 complex is indeed a ribonucleoprotein that binds and processes RNA.
Reason: The Lsm1-7-Pat1 complex is a ribonucleoprotein complex containing RNA-binding Sm domains and functionally interacting with mRNA. This annotation is accurate though the more specific complex identifier (GO:1990726) is more informative.
GO:0005515 protein binding
IPI
PMID:10688190
A comprehensive analysis of protein-protein interactions in ... 		MARK AS OVER ANNOTATED
Summary: IPI evidence from comprehensive protein-protein interaction study. LSM1 interacts with LSM2, LSM3, LSM4, LSM5, LSM6, LSM7 as core members of the Lsm1-7 complex.
Reason: While LSM1 does bind proteins as part of the Lsm1-7 complex, the generic GO:0005515 (protein binding) term is not informative for functional annotation. The specific protein-protein interactions and the biological role (complex assembly for mRNA decay) are better captured by GO:1990726 (Lsm1-7-Pat1 complex). Generic "protein binding" annotations lack functional specificity and should be replaced with mechanistically informative terms that describe what the binding accomplishes.
Proposed replacements: Lsm1-7-Pat1 complex
Supporting Evidence:
PMID:10688190
A comprehensive analysis of protein-protein interactions in Saccharomyces cerevisiae.
GO:0005515 protein binding
IPI
PMID:10900456
Genome-wide protein interaction screens reveal functional ne... 		MARK AS OVER ANNOTATED
Summary: IPI evidence from genome-wide protein interaction screens showing LSM1 interactions with PAT1 and other Lsm proteins.
Reason: Generic protein binding annotation without functional context. LSM1 interacts with other Lsm proteins and PAT1, but this is comprehensively described by the complex component annotation GO:1990726. The generic term provides no insight into the biological significance of these interactions.
Proposed replacements: Lsm1-7-Pat1 complex
Supporting Evidence:
PMID:10900456
Genome-wide protein interaction screens reveal functional networks involving Sm-like proteins.
GO:0005515 protein binding
IPI
PMID:11780629
The DEAD box helicase, Dhh1p, functions in mRNA decapping an... 		MARK AS OVER ANNOTATED
Summary: IPI evidence showing interaction of LSM1 with Dhh1 (DEAD box helicase) documented in interaction studies.
Reason: Generic protein binding term without mechanistic context. While LSM1 does interact with Dhh1, the biological significance and functional consequence are not captured by this vague annotation. The mRNA decay process annotations better describe what these interactions accomplish.
Supporting Evidence:
PMID:11780629
The DEAD box helicase, Dhh1p, functions in mRNA decapping and interacts with both the decapping and deadenylase complexes.
GO:0005515 protein binding
IPI
PMID:11805837
Systematic identification of protein complexes in Saccharomy... 		MARK AS OVER ANNOTATED
Summary: IPI evidence from mass spectrometry studies of protein complexes identifying LSM1 in the Lsm1-7-Pat1 complex.
Reason: Generic protein binding annotation redundant with complex component annotation. The systematic protein complex identification is better represented by GO:1990726.
Proposed replacements: Lsm1-7-Pat1 complex
Supporting Evidence:
PMID:11805837
Systematic identification of protein complexes in Saccharomyces cerevisiae by mass spectrometry.
GO:0005515 protein binding
IPI
PMID:14759368
High-definition macromolecular composition of yeast RNA-proc... 		MARK AS OVER ANNOTATED
Summary: IPI evidence from high-definition macromolecular composition of yeast RNA-processing complexes.
Reason: This annotation documents LSM1 protein interactions from complex characterization studies, but the generic "protein binding" term is uninformative. The complex assembly and function are better captured by specific GO terms.
Proposed replacements: Lsm1-7-Pat1 complex
Supporting Evidence:
PMID:14759368
High-definition macromolecular composition of yeast RNA-processing complexes.
GO:0005515 protein binding
IPI
PMID:16429126
Proteome survey reveals modularity of the yeast cell machine... 		MARK AS OVER ANNOTATED
Summary: IPI evidence from proteome survey identifying LSM1 protein interactions.
Reason: Generic annotation without functional specificity. LSM1 protein interactions are functionally significant only in the context of mRNA decay machinery assembly.
Proposed replacements: Lsm1-7-Pat1 complex
Supporting Evidence:
PMID:16429126
Proteome survey reveals modularity of the yeast cell machinery.
GO:0005515 protein binding
IPI
PMID:16554755
Global landscape of protein complexes in the yeast Saccharom... 		MARK AS OVER ANNOTATED
Summary: IPI evidence from global landscape studies of yeast protein complexes.
Reason: Generic protein binding term redundant with more specific complex component annotation.
Proposed replacements: Lsm1-7-Pat1 complex
Supporting Evidence:
PMID:16554755
Global landscape of protein complexes in the yeast Saccharomyces cerevisiae.
GO:0005515 protein binding
IPI
PMID:18719252
High-quality binary protein interaction map of the yeast int... 		MARK AS OVER ANNOTATED
Summary: IPI evidence from high-quality binary protein interaction mapping.
Reason: Binary protein interactions documented but better represented by complex component annotation.
Proposed replacements: Lsm1-7-Pat1 complex
Supporting Evidence:
PMID:18719252
High-quality binary protein interaction map of the yeast interactome network.
GO:0005515 protein binding
IPI
PMID:23267104
Proteome-wide protein interaction measurements of bacterial ... 		MARK AS OVER ANNOTATED
Summary: IPI evidence from proteome-wide protein interaction measurements.
Reason: Generic binding annotation without functional context.
Proposed replacements: Lsm1-7-Pat1 complex
Supporting Evidence:
PMID:23267104
Proteome-wide protein interaction measurements of bacterial proteins of unknown function.
GO:0005515 protein binding
IPI
PMID:37070168
RNA-dependent interactome allows network-based assignment of... 		MARK AS OVER ANNOTATED
Summary: IPI evidence from RNA-dependent interactome analysis.
Reason: Generic protein binding term lacks functional specificity for RNA-binding protein annotation.
Proposed replacements: Lsm1-7-Pat1 complex
Supporting Evidence:
PMID:37070168
RNA-dependent interactome allows network-based assignment of RNA-binding protein function.
GO:0005515 protein binding
IPI
PMID:37968396
The social and structural architecture of the yeast protein ... 		MARK AS OVER ANNOTATED
Summary: IPI evidence from social and structural architecture study of yeast protein interactome.
Reason: Generic annotation not informative for molecular function annotation.
Proposed replacements: Lsm1-7-Pat1 complex
Supporting Evidence:
PMID:37968396
The social and structural architecture of the yeast protein interactome.
GO:0000290 deadenylation-dependent decapping of nuclear-transcribed mRNA
IMP
PMID:15716506
Mutations in the Saccharomyces cerevisiae LSM1 gene that aff... 		ACCEPT
Summary: IMP evidence from mutagenesis study directly testing LSM1 function in mRNA decapping. Tharun et al. (2005) used point mutations of LSM1 to show impaired mRNA decay and defective decapping.
Reason: This is strong experimental evidence that LSM1 is required for mRNA decapping activation. The mutagenesis study demonstrates that RNA-binding residues are critical for function, confirming the mechanistic role. Duplicate annotation with different evidence codes is appropriate.
Supporting Evidence:
PMID:15716506
Mutations affecting the predicted RNA-binding and inter-subunit interaction residues of Lsm1p led to impairment of mRNA decay, suggesting that the integrity of the Lsm1p-7p complex and the ability of the Lsm1p-7p complex to interact with mRNA are important for mRNA decay function
GO:0000932 P-body
IDA
PMID:12730603
Decapping and decay of messenger RNA occur in cytoplasmic pr... 		ACCEPT
Summary: IDA evidence from immunofluorescence and localization studies showing LSM1 in P-bodies. Sheth & Parker (2003) demonstrated that decapping enzymes and LSM proteins localize to P-bodies.
Reason: Direct observation of LSM1 localization to P-bodies where mRNA decay occurs. This is consistent with IBA and IMP annotations and represents core cellular compartmentalization of LSM1 function.
Supporting Evidence:
PMID:12730603
proteins that activate or catalyze decapping are concentrated in P bodies
GO:0005737 cytoplasm
HDA
PMID:22842922
Dissecting DNA damage response pathways by analysing protein... 		ACCEPT
Summary: HDA (high-throughput direct assay) evidence showing cytoplasmic localization from DNA damage response studies detecting LSM1 in cytoplasm.
Reason: Cytoplasmic localization is well-established and essential for LSM1 function. HDA evidence is high-confidence direct observation. Consistent with other localization evidence.
Supporting Evidence:
PMID:22842922
Dissecting DNA damage response pathways by analysing protein localization and abundance changes during DNA replication stress
GO:1990726 Lsm1-7-Pat1 complex
IDA
PMID:24139796
Architecture of the Lsm1-7-Pat1 complex: a conserved assembl... 		ACCEPT
Summary: IDA evidence from crystal structure showing LSM1 as core subunit of the Lsm1-7-Pat1 complex. Sharif & Conti (2013) provided 2.3 Γ… structure demonstrating complex architecture.
Reason: The crystal structure provides definitive evidence of LSM1 as a core component of the Lsm1-7-Pat1 complex. This is the highest quality structural evidence and confirms mechanistic details of complex assembly.
Supporting Evidence:
PMID:24139796
The 2.3 Γ… resolution structure of S. cerevisiae Lsm1-7 shows the presence of a heptameric ring
GO:0003729 mRNA binding
IDA
PMID:23222640
Global analysis of yeast mRNPs. 		ACCEPT
Summary: IDA evidence from global analysis of yeast mRNPs (messenger ribonucleoprotein particles) showing LSM1 associated with mRNA.
Reason: Direct evidence of LSM1 in mRNP complexes confirms functional mRNA binding. Consistent with IBA annotation and structural data showing RNA binding pocket.
Supporting Evidence:
PMID:23222640
Global analysis of yeast mRNPs
GO:0003682 chromatin binding
IDA
PMID:23706738
Gene expression is circular: factors for mRNA degradation al... 		REMOVE
Summary: IDA evidence from localization study reporting LSM1 chromatin binding. However, this annotation may reflect contamination or indirect association rather than true chromatin binding.
Reason: LSM1 is an mRNA decay protein, not primarily a chromatin-binding protein. The Lsm1-7 complex functions in the cytoplasm and at P-bodies on mRNA transcripts, not at chromatin. The annotation from PMID:23706738 appears to report LSM1 in nuclei and potentially binding to chromatin during the "Gene expression is circular" studies, but this is not a core function. LSM1 does not have characteristic chromatin-binding domains. This annotation likely represents mislocalization or experimental artifact and should not be retained.
Supporting Evidence:
PMID:23706738
Gene expression is circular: factors for mRNA degradation also foster mRNA synthesis.
GO:0005634 nucleus
IDA
PMID:23706738
Gene expression is circular: factors for mRNA degradation al... 		ACCEPT
Summary: IDA evidence showing nuclear localization from the "Gene expression is circular" study. LSM1 is detected in both nucleus and cytoplasm.
Reason: Consistent with UniProt annotation showing nuclear localization. While cytoplasmic mRNA decay is the primary function, nuclear detection is documented. Acceptable to retain.
Supporting Evidence:
PMID:23706738
Gene expression is circular: factors for mRNA degradation also foster mRNA synthesis.
GO:0005737 cytoplasm
IDA
PMID:23706738
Gene expression is circular: factors for mRNA degradation al... 		ACCEPT
Summary: IDA evidence confirming cytoplasmic localization from direct observation studies.
Reason: Cytoplasm is the primary site of LSM1 function. Direct observation confirms expected localization.
Supporting Evidence:
PMID:23706738
Gene expression is circular: factors for mRNA degradation also foster mRNA synthesis.
GO:0000288 nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay
IMP
PMID:10747033
A Sm-like protein complex that participates in mRNA degradat... 		ACCEPT
Summary: IMP evidence from Bouveret et al. (2000) directly demonstrating LSM1 involvement in deadenylation-dependent mRNA decay through deletion analysis.
Reason: LSM1 deletion mutants showed increased mRNA half-life and accumulation of capped mRNAs, demonstrating a block in the decapping step. This is the seminal paper identifying the Lsm1-7 complex role in mRNA decay. Core functional annotation.
Supporting Evidence:
PMID:10747033
Deletions of LSM1, 6, 7 and PAT1 genes increased the half-life of reporter mRNAs. Interestingly, accumulating mRNAs were capped, suggesting a block in mRNA decay at the decapping step.
GO:0000290 deadenylation-dependent decapping of nuclear-transcribed mRNA
IMP
PMID:10761922
Yeast Sm-like proteins function in mRNA decapping and decay. 		ACCEPT
Summary: IMP evidence from Tharun et al. (2000) showing LSM1-Lsm7 mutations inhibit mRNA decapping and demonstrating interaction with decapping machinery.
Reason: Tharun et al. demonstrated that lsm mutations specifically block mRNA decapping, and that Lsm proteins co-immunoprecipitate with Dcp1 and mRNA. This establishes the mechanistic link between LSM1 and decapping activation. Duplicate IMP annotation with different PMID is appropriate as it provides additional mechanistic detail.
Supporting Evidence:
PMID:10761922
mutations in seven yeast Lsm proteins (Lsm1-Lsm7) also lead to inhibition of mRNA decapping
GO:0000932 P-body
IMP
PMID:12730603
Decapping and decay of messenger RNA occur in cytoplasmic pr... 		ACCEPT
Summary: IMP evidence showing P-body function in mRNA decay where LSM1 acts as part of the decapping and decay machinery.
Reason: While primarily a localization annotation (IDA also exists for same PMID), the IMP evidence demonstrates that P-body function in mRNA decay is dependent on the decapping machinery where LSM1 operates. Both evidence types are valid and appropriate.
Supporting Evidence:
PMID:12730603
A major pathway of eukaryotic messenger RNA (mRNA) turnover begins with deadenylation, followed by decapping and 5' to 3' exonucleolytic decay
GO:0000932 P-body
IDA
PMID:18611963
A role for Q/N-rich aggregation-prone regions in P-body loca... 		ACCEPT
Summary: IDA evidence showing LSM1 localization to P-bodies in studies of Q/N-rich aggregation-prone regions required for P-body localization.
Reason: Direct observation of LSM1 in P-bodies. This annotation is consistent with other P-body localization evidence. Duplicate IDA annotations with different PMIDs are acceptable as they represent independent observations.
Supporting Evidence:
PMID:18611963
A role for Q/N-rich aggregation-prone regions in P-body localization
GO:0005737 cytoplasm
IDA
PMID:18029398
Requirements for nuclear localization of the Lsm2-8p complex... 		ACCEPT
Summary: IDA evidence from studies of Lsm2-8 nuclear complex showing that LSM1-7 cytoplasmic complex has different localization than its U6-binding counterpart.
Reason: Direct evidence of LSM1-7 cytoplasmic localization, demonstrating distinction from nuclear Lsm2-8 complex. Consistent with other cytoplasmic localization evidence.
Supporting Evidence:
PMID:18029398
Requirements for nuclear localization of the Lsm2-8p complex and competition between nuclear and cytoplasmic Lsm complexes

Core Functions

LSM1 binds mRNA through its Sm domain, specifically recognizing poly(U) tracts at the 3' end of deadenylated mRNAs. This RNA binding is essential for the activation of decapping and represents a core catalytic property of LSM1. LSM1 functions as part of the Lsm1-7-Pat1 complex where it plays the defining role in mRNA decay activation through deadenylation-dependent decapping and 5' to 3' exonucleolytic degradation.

Molecular Function:
mRNA binding
Directly Involved In:
deadenylation-dependent decapping of nuclear-transcribed mRNA nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay
Cellular Locations:
cytoplasm P-body
Supporting Evidence:
  • file:yeast/LSM1/LSM1-deep-research-falcon.md
    LSM1 encodes Lsm1p, the defining subunit of the cytoplasmic Lsm1-7 ring that partners with Pat1 to recognize deadenylated mRNAs and promote decapping and 5' to 3' mRNA decay.

References

file:yeast/LSM1/LSM1-deep-research-falcon.md
Falcon deep research report for LSM1
  • Falcon supports LSM1 as the defining cytoplasmic Lsm1-7-Pat1 complex subunit coupling deadenylated mRNA recognition to decapping and 5' to 3' decay.
    "The Lsm1-7 ring plus Pat1 is a key module that links 3' end status to decapping: Pat1/Lsm1-7 binds oligoadenylated 3' ends and helps recruit/activate the decapping enzyme."
GO_REF:0000002
Gene Ontology annotation through association of InterPro records with GO terms
GO_REF:0000033
Annotation inferences using phylogenetic trees
GO_REF:0000043
Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
GO_REF:0000044
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
GO_REF:0000117
Electronic Gene Ontology annotations created by ARBA machine learning models
GO_REF:0000120
Combined Automated Annotation using Multiple IEA Methods
PMID:10688190
A comprehensive analysis of protein-protein interactions in Saccharomyces cerevisiae.
PMID:10747033
A Sm-like protein complex that participates in mRNA degradation.
PMID:10761922
Yeast Sm-like proteins function in mRNA decapping and decay.
PMID:10900456
Genome-wide protein interaction screens reveal functional networks involving Sm-like proteins.
PMID:11780629
The DEAD box helicase, Dhh1p, functions in mRNA decapping and interacts with both the decapping and deadenylase complexes.
PMID:11805837
Systematic identification of protein complexes in Saccharomyces cerevisiae by mass spectrometry.
PMID:12730603
Decapping and decay of messenger RNA occur in cytoplasmic processing bodies.
PMID:14759368
High-definition macromolecular composition of yeast RNA-processing complexes.
PMID:15716506
Mutations in the Saccharomyces cerevisiae LSM1 gene that affect mRNA decapping and 3' end protection.
PMID:16429126
Proteome survey reveals modularity of the yeast cell machinery.
PMID:16554755
Global landscape of protein complexes in the yeast Saccharomyces cerevisiae.
PMID:18029398
Requirements for nuclear localization of the Lsm2-8p complex and competition between nuclear and cytoplasmic Lsm complexes.
PMID:18611963
A role for Q/N-rich aggregation-prone regions in P-body localization.
PMID:18719252
High-quality binary protein interaction map of the yeast interactome network.
PMID:22842922
Dissecting DNA damage response pathways by analysing protein localization and abundance changes during DNA replication stress.
PMID:23222640
Global analysis of yeast mRNPs.
PMID:23267104
Proteome-wide protein interaction measurements of bacterial proteins of unknown function.
PMID:23706738
Gene expression is circular: factors for mRNA degradation also foster mRNA synthesis.
PMID:24139796
Architecture of the Lsm1-7-Pat1 complex: a conserved assembly in eukaryotic mRNA turnover.
PMID:37070168
RNA-dependent interactome allows network-based assignment of RNA-binding protein function.
PMID:37968396
The social and structural architecture of the yeast protein interactome.

Deep Research

Falcon

(LSM1-deep-research-falcon.md)
Comprehensive research report: **Saccharomyces cerevisiae LSM1** (UniProt **P47017**, aka **SPB8**, locus **YJL124C**) Falcon Edison Scientific Literature 39 citations 2026-05-11T07:49:02.661910

The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.

You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.

We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.

We are interested in where in or outside the cell the gene product carries out its function.

We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.

Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.

Comprehensive research report: Saccharomyces cerevisiae LSM1 (UniProt P47017, aka SPB8, locus YJL124C)

Executive summary

LSM1 encodes Lsm1p, the defining subunit of the cytoplasmic Lsm1–7 ring that partners with Pat1 to recognize deadenylated (oligoadenylated) mRNAs and promote 5β€²-cap removal (decapping) and subsequent 5β€²β†’3β€² mRNA decay by Xrn1. The Lsm1–7/Pat1 assembly is enriched in processing bodies (P-bodies) but contemporary evidence and expert synthesis emphasize that much decapping occurs co-translationally on polyribosomes, not necessarily inside P-bodies. Recent work (2023–2024) refines the classic β€œdeadenylation triggers decapping” model by providing structural/biochemical detail for Lsm1–7–Pat1 recognition of 3β€² ends, highlighting Dcp2 regulatory motifs targeted by Pat1/Scd6, quantifying large transcript sets controlled by Pat1/Dhh1/Lsm1, and expanding roles for Pat1/Lsm1–7 in nutrient signaling and autophagy via context-dependent 3β€²-end protection of selected ATG transcripts. (tharun2005mutationsinthe pages 2-3, he2023eukaryoticmrnadecapping pages 3-4, zhao2023structureandfunction pages 8-10, he2023eukaryoticmrnadecapping pages 8-9, he2023eukaryoticmrnadecapping pages 17-19)

1) Target verification and gene/protein identity (mandatory disambiguation)

Verified identity

The literature examined here explicitly concerns Saccharomyces cerevisiae Lsm1p, a member of the Sm-like (Lsm) protein family that forms a cytoplasmic heptameric Lsm1–7 complex and acts in cytoplasmic mRNA turnover. This is distinct from the nuclear Lsm2–8 ring (Lsm2–8) that functions in U6 snRNP biology and splicing. (tharun2005mutationsinthe pages 2-3, tharun2005mutationsinthe pages 1-2, daugeron2001theyeastpop2 pages 1-2)

Key distinction preventing ambiguity

  • Cytoplasmic complex: Lsm1 is the distinguishing subunit of Lsm1–7; this ring functions in mRNA decapping/decay. (tharun2005mutationsinthe pages 2-3, tharun2005mutationsinthe pages 1-2)
  • Nuclear complex: Lsm2–8 is a separate ring functioning in the nucleus (U6 snRNP), and is not the primary decapping activator complex. (tharun2005mutationsinthe pages 2-3)

2) Key concepts and definitions (current understanding)

2.1 mRNA decapping and 5β€²β†’3β€² decay

Decapping is the enzymatic removal of the 5β€² cap structure from an mRNA, an event that commits the transcript to 5β€²β†’3β€² exonucleolytic degradation (primarily by Xrn1) and terminates its functional lifespan. In yeast, decapping is executed by a single Dcp1–Dcp2 enzyme whose targeting and activation depend on multiple β€œdecapping activators,” including Pat1 and the Lsm1–7 complex. (he2023eukaryoticmrnadecapping pages 1-3, he2023eukaryoticmrnadecapping pages 3-4)

2.2 Deadenylation-coupled decapping and the Lsm1–7–Pat1 module

A classical model is that decapping generally follows deadenylation, with poly(A) tails reduced to ~10 nt before efficient decapping. Within this framework, the Lsm1–7 ring plus Pat1 is a key module that links 3β€²-end status to decapping: Pat1/Lsm1–7 binds oligoadenylated 3β€² ends and helps recruit/activate the decapping enzyme. (he2023eukaryoticmrnadecapping pages 3-4, zhao2023structureandfunction pages 1-2)

2.3 P-bodies as cytoplasmic mRNP assemblies

P-bodies are cytoplasmic foci enriched in decapping machinery (Dcp1/Dcp2), decapping activators (including Lsm1–7 and Pat1), Xrn1, and decay-targeted mRNAs. They are widely used as readouts of mRNP remodeling and mRNA repression/decay states. (sheth2006targetingofaberrant pages 1-3, tharun2005mutationsinthe pages 9-10)

3) Primary molecular function of Lsm1p (what it does)

3.1 Primary function: decapping activation and coupling to 5β€²β†’3β€² decay

Genetic and biochemical evidence establishes that the Lsm1–7 complex is a general activator of decapping in the major yeast 5β€²β†’3β€² mRNA degradation pathway and that it associates (directly or via RNP bridging) with other decay factors including Pat1, Dhh1, Dcp1/Dcp2, and Xrn1. (tharun2005mutationsinthe pages 1-2, daugeron2001theyeastpop2 pages 1-2)

3.2 3β€²-end protection of deadenylated mRNAs

In addition to promoting decapping, Lsm1–7 contributes to protecting 3β€² ends of deadenylated mRNAs from 3β€² trimming, consistent with a model in which the ring binds the 3β€² end of deadenylated substrates. Co-immunoprecipitation evidence shows Lsm proteins associate with deadenylated mRNA decay intermediates in vivo, supporting direct substrate engagement. (tharun2005mutationsinthe pages 1-2, tharun2005mutationsinthe pages 12-13)

4) Cellular localization and where the protein carries out its function

4.1 Cytoplasmic localization and P-body association

Lsm1p (and Lsm1–7) is a cytoplasmic factor that localizes to P-bodies, which are enriched for decapping/5β€²β†’3β€² decay factors. Loss of LSM1 disrupts P-body recruitment of other Lsm subunits, showing Lsm1’s importance for Lsm1–7 behavior in these cytoplasmic assemblies. (tharun2005mutationsinthe pages 9-10, sheth2006targetingofaberrant pages 1-3)

4.2 Expert synthesis: decapping often occurs on polyribosomes, not necessarily in P-bodies

A prominent recent synthesis highlights that many decapping activators (including Pat1/Lsm1–7) and decay enzymes are largely polyribosome-associated, and decapping can occur even when ribosomes are stalled on mRNAs (e.g., cycloheximide conditions). This supports a co-translational decapping paradigm and motivates caution in interpreting P-bodies as the main sites of decapping. (he2023eukaryoticmrnadecapping pages 17-19)

5) Mechanism: how Lsm1 works (structure–function, binding specificity, interactions)

5.1 Architecture: Lsm1–7 is a heptameric Sm-like ring

Reviews synthesizing structural data describe Lsm1–7 as a circular, heptameric Sm-ring that binds RNA. (he2023eukaryoticmrnadecapping pages 3-4)

5.2 RNA recognition: oligoadenylated 3β€² ends and U-rich regions

Structural/biochemical evidence indicates that:
- Lsm1–7 binds near the mRNA 3β€² end and specifically recognizes short oligo(A) tails.
- Adding Pat1 increases affinity for oligo(A) RNA; the assembled Lsm1–7–Pat1 module also shows a preference for U-rich sequences near the 3β€² end. (he2023eukaryoticmrnadecapping pages 3-4, zhao2023structureandfunction pages 8-10)

5.3 The Lsm1 C-terminal extension modulates RNA binding

A 2023 structural review notes that yeast Lsm1 has a distinctive C-terminal extension that forms an extended helix and can occlude the central opening of the ring; deleting this extension increases RNA-binding affinity, implying autoinhibitory or regulatory tuning of RNA engagement. (zhao2023structureandfunction pages 8-10)

5.4 Genetic evidence: Lsm1 Sm-domain residues and C-terminus are required for decay and 3β€² protection

Targeted mutagenesis mapped essential functions to:
- Sm-like core residues predicted to contact RNA and to mediate inter-subunit contacts (ring integrity), which are required for decapping and 3β€²-end protection.
- The unique C-terminal region (∼61 aa) of Lsm1, where deletions or even a C-terminal tag disrupt decay/3β€² protection, indicating functional specificity beyond the conserved Sm fold. (tharun2005mutationsinthe pages 6-8, tharun2005mutationsinthe pages 2-3)

5.5 Recruitment model: Pat1 bridges Lsm1–7 to the decapping enzyme and Xrn1

Mechanistic synthesis in 2023 proposes that:
- The Lsm1–7 ring makes direct contacts with Pat1.
- Pat1 has multi-domain interactions: its C-terminal region binds Dcp2 and Xrn1, while its M/C regions bind Lsm1–7.
- Pat1/Lsm1–7 has strong RNA-binding and a preference for oligoadenylated RNAs, supporting a model where Pat1/Lsm1–7 binds oligoadenylated 3β€² ends and recruits decapping and downstream 5β€²β†’3β€² decay factors. (he2023eukaryoticmrnadecapping pages 3-4, zhao2023structureandfunction pages 8-10)

5.6 Visual model support from recent review figures

Figure panels extracted from He & Jacobson (2023) schematically depict Pat1 interacting with the Lsm1–7 ring and placing the Pat1/Lsm1 module as a targeting component that directs assembly of an active decapping complex on specific substrates. (he2023eukaryoticmrnadecapping media 2ef221cc, he2023eukaryoticmrnadecapping media 0259c12e)

6) Recent developments and latest research (prioritizing 2023–2024)

6.1 Transcriptome-scale targeting: Pat1/Dhh1 (and overlap with Lsm1)

A 2023 mechanistic review summarizes that Pat1 and Lsm1 share a large fraction of endogenous targets (~84% overlap), and that Dhh1/Pat1/Lsm1 together regulate 1,587 transcripts, emphasizing that decapping activators impose transcript-selective regulation rather than only global turnover control. (he2023eukaryoticmrnadecapping pages 8-9)

6.2 Multi-omics evidence linking decapping activators to nutrient response programs

A 2023 yeast study used ribosome profiling, RNA-seq, CAGE (capped mRNAs), Pol II ChIP-seq, and quantitative proteomics to show that Pat1 and Dhh1 tune cellular responses to nutrient availability by controlling both mRNA turnover and translation. Quantitative results include:
- 747 mRNAs upregulated in pat1Ξ” and 982 upregulated in pat1Ξ” dhh1Ξ” (cutoff >1.5-fold, FDR < 0.05), indicating broad transcriptome effects.
- A ~25% reduction in polysome/monosome ratio in pat1Ξ” and ~40% in the double mutant, consistent with broad translation changes.
- Pathway-specific sets including 61 cell wall/agglutinin mRNAs, 51 oxidative phosphorylation transcripts, and 83 carbon catabolite repressed mRNAs, reflecting coordinated post-transcriptional control of metabolic programs. (vijjamarri2023mrnadecappingactivators pages 7-8, vijjamarri2023mrnadecappingactivators pages 16-17, vijjamarri2023mrnadecappingactivators pages 15-16)

Although this study centers on Pat1/Dhh1, its conclusions are relevant to Lsm1 because Pat1’s decapping function is mechanistically coupled to Lsm1–7 recruitment to oligoadenylated mRNAs and their joint roles in decapping activation. (he2023eukaryoticmrnadecapping pages 3-4, vijjamarri2023mrnadecappingactivators pages 1-2)

6.3 Context-dependent β€œprotective” role of Pat1/Lsm1–7 in autophagy (2023 synthesis)

A major conceptual refinement is that Pat1/Lsm1–7 can stabilize subsets of transcripts under specific physiological states. During nitrogen starvation–induced autophagy, Pat1 dephosphorylation promotes binding to select ATG mRNAs, and Pat1/Lsm1–7 protects these mRNAs from exosome-mediated 3β€²β†’5β€² decay (with rescue by Ski3 loss), supporting their accumulation and translation for robust autophagy. (he2023eukaryoticmrnadecapping pages 17-19)

6.4 2023–2024: Decapping/autophagy/ageing as a model application area

A 2023 study of LSM mutants links lsm1Ξ” and LSM4 perturbations to defects in autophagy induction and ageing-associated phenotypes, framing the Pat1–Lsm module as important for stabilizing certain ATG mRNAs during starvation. (caraba2023yeastlsmproapoptotica pages 8-10)

A 2024 review-like synthesis explicitly positions yeast decapping mutants (including lsm1Ξ” contexts) as model systems for ageing and autophagy, describing assays such as GFP-Atg8 flux readouts and rapamycin sensitivity as tractable implementations for connecting mRNA turnover to longevity pathways. (caraba2024yeastdecappingmutants pages 1-5, caraba2024yeastdecappingmutants pages 17-22)

7) Current applications and real-world implementations

7.1 Yeast as a platform for mechanistic dissection of mRNA decay and quality control

Yeast remains a premier system for dissecting cytoplasmic mRNA decay and quality control pathways, including NMD, using genetically tractable decapping and P-body component mutants to β€œtrap” decay intermediates and visualize compartmentalization. Classic implementations include GFP/RFP-tagging of decapping activators (including Lsm1) and reporter mRNAs engineered with RNA-binding sites to visualize their recruitment to P-bodies. (sheth2006targetingofaberrant pages 1-3)

7.2 High-throughput and quantitative systems biology pipelines (2023)

Modern β€œreal-world” implementation in basic research includes integrated multi-omics pipelines (Ribo-seq, RNA-seq, CAGE, Pol II ChIP-seq, quantitative proteomics) to quantify how decapping activators shape transcript levels and protein output under different nutrient conditions. (vijjamarri2023mrnadecappingactivators pages 1-2)

7.3 Condensate biology and phase separation as an application context

Decapping/P-body factors intersect with biomolecular condensate biology. For example, an imaging-based screen and follow-up mechanistic work showed Lsm7 can form phase-separated condensates that seed stress granule formation, demonstrating how Lsm complexes (including the Lsm1–7/Pat1 module) are studied at the interface of RNA turnover and LLPS-driven stress responsesβ€”an area relevant to ageing and disease mechanisms. (lindstrom2022lsm7phaseseparatedcondensates pages 1-2)

7.4 Autophagy/ageing models (2023–2024)

Yeast decapping mutants are applied as model systems for autophagy and lifespan research, with readouts such as rapamycin sensitivity, GFP-Atg8 processing, and stress resistance phenotyping used to evaluate how mRNA turnover machinery influences cellular maintenance pathways. (caraba2024yeastdecappingmutants pages 1-5, caraba2023yeastlsmproapoptotica pages 8-10)

8) Expert opinions and authoritative analysis (selected themes)

8.1 Reframing P-bodies as not necessarily primary decay sites

An authoritative 2023 review emphasizes that P-bodies contain thousands of mRNAs and many decay factors, but argues that technical artifacts (e.g., MS2-based imaging approaches) and multiple lines of biochemical evidence support a view that P-bodies are not major sites of decapping; rather, decapping is often coupled to translation on polyribosomes. This informs how Lsm1 localization to P-bodies should be interpreted: enrichment does not necessarily imply that decapping occurs exclusively (or even mainly) within P-bodies. (he2023eukaryoticmrnadecapping pages 17-19)

8.2 Lsm1–7/Pat1 as a context-dependent regulator (decay vs protection)

Recent synthesis highlights dual functionality: Pat1/Lsm1–7 is classically a decapping activator (loss stabilizes mRNAs) but can also protect specific mRNAs from 3β€²β†’5β€² decay under starvation by binding and shielding their 3β€² ends. This duality positions Lsm1 not as a simple β€œdecay factor,” but as an mRNP remodeling module whose outcome depends on physiological context and competing decay routes. (he2023eukaryoticmrnadecapping pages 17-19)

9) Statistics and data highlights (recent studies)

  • Targeting overlap: Pat1 and Lsm1 share ~84% overlap in endogenous targets; Dhh1/Pat1/Lsm1 together regulate 1,587 transcripts (review synthesis). (he2023eukaryoticmrnadecapping pages 8-9)
  • Transcriptome perturbation by decapping activators: In pat1Ξ”, 747 mRNAs up and 2024 down; in pat1Ξ” dhh1Ξ”, 982 up and 1052 down (RNA-seq thresholds >1.5-fold, FDR < 0.05). (vijjamarri2023mrnadecappingactivators pages 7-8)
  • Translation-state readout: Polysome/monosome ratio decreased by ~25% in pat1Ξ” and ~40% in pat1Ξ” dhh1Ξ”. (vijjamarri2023mrnadecappingactivators pages 7-8)
  • Pathway-specific sets: examples include 61 cell wall/agglutinin mRNAs, 51 oxidative phosphorylation transcripts, and 83 carbon catabolite repressed mRNAs affected in Pat1/Dhh1 perturbations, indicating pathway-selective post-transcriptional control. (vijjamarri2023mrnadecappingactivators pages 16-17, vijjamarri2023mrnadecappingactivators pages 15-16)

10) Evidence map (table)

The following table consolidates evidence-backed functional annotation elements (identity, complex membership, mechanism, localization, pathways, and quantitative findings):

Aspect Key findings (1-2 sentences) Representative sources (include author-year, venue) URL/DOI Publication date
Identity/complex The target matches Saccharomyces cerevisiae Lsm1/Spb8 (UniProt P47017), the distinguishing subunit of the cytoplasmic heteroheptameric Lsm1–7 complex, which is functionally distinct from the nuclear Lsm2–8 complex involved in U6 snRNP/pre-mRNA splicing (tharun2005mutationsinthe pages 2-3, tharun2005mutationsinthe pages 1-2, daugeron2001theyeastpop2 pages 1-2). Tharun et al. 2005, Genetics; Daugeron et al. 2001, Nucleic Acids Research https://doi.org/10.1534/genetics.104.034322; https://doi.org/10.1093/nar/29.12.2448 May 2005; Jun 2001
Molecular function Lsm1 functions in the major cytoplasmic 5β€²β†’3β€² mRNA decay pathway as part of Pat1/Lsm1–7, acting as a general decapping activator and also contributing to 3β€²-end protection of deadenylated mRNAs before Xrn1-mediated degradation (tharun2005mutationsinthe pages 1-2, he2023eukaryoticmrnadecapping pages 3-4, zhao2023structureandfunction pages 1-2). Tharun et al. 2005, Genetics; He & Jacobson 2023, The FEBS Journal; Zhao et al. 2023, Frontiers in Genetics https://doi.org/10.1534/genetics.104.034322; https://doi.org/10.1111/febs.16626; https://doi.org/10.3389/fgene.2023.1233842 May 2005; Sep 2023; Oct 2023
RNA-binding specificity Structural/biochemical work indicates the Lsm1–7 ring binds near mRNA 3β€² ends, with preference for short oligoadenylated tails; addition of Pat1 increases affinity for oligo(A) RNA, and the assembled complex also shows preference for U-rich sequences near the 3β€² end (he2023eukaryoticmrnadecapping pages 3-4, zhao2023structureandfunction pages 8-10). He & Jacobson 2023, The FEBS Journal; Zhao et al. 2023, Frontiers in Genetics https://doi.org/10.1111/febs.16626; https://doi.org/10.3389/fgene.2023.1233842 Sep 2023; Oct 2023
Interaction partners Lsm1–7 physically/functionally associates with Pat1, Dhh1, Dcp1/Dcp2, and Xrn1; Pat1 is the main bridge to decapping machinery, with Pat1 C-terminal regions binding Dcp2 and Xrn1 while Pat1 also contacts the Lsm1–7 ring (he2023eukaryoticmrnadecapping pages 3-4, zhao2023structureandfunction pages 8-10, daugeron2001theyeastpop2 pages 1-2). He & Jacobson 2023, The FEBS Journal; Zhao et al. 2023, Frontiers in Genetics; Daugeron et al. 2001, Nucleic Acids Research https://doi.org/10.1111/febs.16626; https://doi.org/10.3389/fgene.2023.1233842; https://doi.org/10.1093/nar/29.12.2448 Sep 2023; Oct 2023; Jun 2001
Localization Lsm1 is a P-body-associated cytoplasmic factor. P-bodies contain decapping enzymes, decapping activators including Lsm1–7, and Xrn1; Lsm1 is required for efficient recruitment/stability of other Lsm subunits at P-bodies, although some RNA-binding mutants still localize there (sheth2006targetingofaberrant pages 1-3, tharun2005mutationsinthe pages 9-10, lindstrom2022lsm7phaseseparatedcondensates pages 1-2). Sheth & Parker 2006, Cell; Tharun et al. 2005, Genetics; LindstrΓΆm et al. 2022, Nature Communications https://doi.org/10.1016/j.cell.2006.04.037; https://doi.org/10.1534/genetics.104.034322; https://doi.org/10.1038/s41467-022-31282-8 Jun 2006; May 2005; Jun 2022
Pathways/phenotypes Beyond basal mRNA turnover, Pat1/Lsm1–7 has a context-dependent protective role in autophagy: during nitrogen starvation, Pat1/Lsm1–7 binds specific ATG mRNAs and protects them from exosome-mediated 3β€²β†’5β€² decay, supporting autophagy induction; lsm1-related decapping defects are also linked to ageing/autophagy phenotypes in yeast models (he2023eukaryoticmrnadecapping pages 17-19, caraba2023yeastlsmproapoptotica pages 8-10). He & Jacobson 2023, The FEBS Journal; Caraba et al. 2023, International Journal of Molecular Sciences https://doi.org/10.1111/febs.16626; https://doi.org/10.3390/ijms241813708 Sep 2023; Sep 2023
Quantitative stats 2023-2024 Recent yeast decapping studies cited in the evidence report that Pat1 and Lsm1 share ~84% overlap in endogenous targets, while Dhh1/Pat1/Lsm1 together regulate 1,587 transcripts; independent 2023 systems analyses of Pat1/Dhh1 mutants found 747 mRNAs upregulated in pat1Ξ”, 982 up in pat1Ξ” dhh1Ξ”, ~25% lower polysome/monosome ratio in pat1Ξ”, and pathway-specific sets such as 61 cell wall/agglutinin mRNAs, 51 oxidative phosphorylation mRNAs, and 83 carbon-catabolite-repressed mRNAs (he2023eukaryoticmrnadecapping pages 8-9, vijjamarri2023mrnadecappingactivators pages 16-17, vijjamarri2023mrnadecappingactivators pages 15-16, vijjamarri2023mrnadecappingactivators pages 7-8). He & Jacobson 2023, The FEBS Journal; Vijjamarri et al. 2023, Nucleic Acids Research https://doi.org/10.1111/febs.16626; https://doi.org/10.1093/nar/gkad584 Sep 2023; Jul 2023
Key experimental evidence Evidence includes targeted mutagenesis of predicted RNA-binding/inter-subunit residues in Lsm1, mRNA decay reporter assays (MFA2pG fragment accumulation and half-life measurements), co-immunoprecipitation with deadenylated mRNPs, fluorescence microscopy of P-bodies, and more recent structural/biochemical analyses showing a heptameric ring with an Lsm1 C-terminal extension that modulates RNA binding (zhao2023structureandfunction pages 8-10, tharun2005mutationsinthe pages 6-8, tharun2005mutationsinthe pages 2-3, tharun2005mutationsinthe pages 12-13). Zhao et al. 2023, Frontiers in Genetics; Tharun et al. 2005, Genetics https://doi.org/10.3389/fgene.2023.1233842; https://doi.org/10.1534/genetics.104.034322 Oct 2023; May 2005

Table: This table summarizes evidence-supported functional annotation for Saccharomyces cerevisiae Lsm1/Spb8 (UniProt P47017), including its complex membership, mechanistic role in mRNA decay, localization, and recent quantitative findings. It is useful as a compact evidence map for the gene’s primary function and pathway context.

11) Limitations and scope notes

  • The provided evidence base includes strong yeast-specific foundational work and several 2023–2024 sources, but some 2023–2024 transcriptome-scale statistics are reported primarily for Pat1/Dhh1 mutants, with Lsm1-specific modern multi-omics datasets not directly extracted here; nevertheless, Pat1 and Lsm1 are mechanistically coupled as the Pat1/Lsm1–7 module, and authoritative synthesis explicitly links their shared targeting and function. (he2023eukaryoticmrnadecapping pages 3-4, he2023eukaryoticmrnadecapping pages 8-9, vijjamarri2023mrnadecappingactivators pages 1-2)
  • Some 2024 content used here appears as a review/preprint-like source with incomplete bibliographic metadata (β€œUnknown journal”), so its claims were used primarily where consistent with, and supported by, peer-reviewed primary/review literature. (caraba2024yeastdecappingmutants pages 1-5, caraba2024yeastdecappingmutants pages 17-22)

Key references (URLs; publication dates)

  • He F, Jacobson A. The FEBS Journal. Sep 2023. β€œEukaryotic mRNA decapping factors: molecular mechanisms and activity.” https://doi.org/10.1111/febs.16626 (he2023eukaryoticmrnadecapping pages 1-3, he2023eukaryoticmrnadecapping pages 3-4, he2023eukaryoticmrnadecapping pages 17-19)
  • Zhao Q et al. Frontiers in Genetics. Oct 2023. β€œStructure and function of molecular machines involved in deadenylation-dependent 5β€²-3β€² mRNA degradation.” https://doi.org/10.3389/fgene.2023.1233842 (zhao2023structureandfunction pages 8-10)
  • Vijjamarri AK et al. Nucleic Acids Research. Jul 2023. β€œmRNA decapping activators Pat1 and Dhh1 regulate transcript abundance and translation to tune cellular responses to nutrient availability.” https://doi.org/10.1093/nar/gkad584 (vijjamarri2023mrnadecappingactivators pages 7-8, vijjamarri2023mrnadecappingactivators pages 16-17)
  • Tharun S et al. Genetics. May 2005. β€œMutations in the S. cerevisiae LSM1 Gene That Affect mRNA Decapping and 3β€² End Protection.” https://doi.org/10.1534/genetics.104.034322 (tharun2005mutationsinthe pages 1-2, tharun2005mutationsinthe pages 6-8)
  • Sheth U, Parker R. Cell. Jun 2006. β€œTargeting of Aberrant mRNAs to Cytoplasmic Processing Bodies.” https://doi.org/10.1016/j.cell.2006.04.037 (sheth2006targetingofaberrant pages 1-3)
  • Caraba B et al. International Journal of Molecular Sciences. Sep 2023. β€œYeast Lsm Pro-Apoptotic Mutants Show Defects in Autophagy.” https://doi.org/10.3390/ijms241813708 (caraba2023yeastlsmproapoptotica pages 8-10)

References

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  3. (zhao2023structureandfunction pages 8-10): Qi Zhao, Lorenzo Pavanello, Mark Bartlam, and Gerlof Sebastiaan Winkler. Structure and function of molecular machines involved in deadenylation-dependent 5β€²-3β€² mrna degradation. Frontiers in Genetics, Oct 2023. URL: https://doi.org/10.3389/fgene.2023.1233842, doi:10.3389/fgene.2023.1233842. This article has 14 citations and is from a peer-reviewed journal.

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  10. (sheth2006targetingofaberrant pages 1-3): Ujwal Sheth and Roy Parker. Targeting of aberrant mrnas to cytoplasmic processing bodies. Cell, 125:1095-1109, Jun 2006. URL: https://doi.org/10.1016/j.cell.2006.04.037, doi:10.1016/j.cell.2006.04.037. This article has 385 citations and is from a highest quality peer-reviewed journal.

  11. (tharun2005mutationsinthe pages 9-10): Sundaresan Tharun, Denise Muhlrad, Ashis Chowdhury, and Roy Parker. Mutations in the saccharomyces cerevisiae lsm1 gene that affect mrna decapping and 3β€² end protection. Genetics, 170:33-46, May 2005. URL: https://doi.org/10.1534/genetics.104.034322, doi:10.1534/genetics.104.034322. This article has 78 citations and is from a domain leading peer-reviewed journal.

  12. (tharun2005mutationsinthe pages 12-13): Sundaresan Tharun, Denise Muhlrad, Ashis Chowdhury, and Roy Parker. Mutations in the saccharomyces cerevisiae lsm1 gene that affect mrna decapping and 3β€² end protection. Genetics, 170:33-46, May 2005. URL: https://doi.org/10.1534/genetics.104.034322, doi:10.1534/genetics.104.034322. This article has 78 citations and is from a domain leading peer-reviewed journal.

  13. (tharun2005mutationsinthe pages 6-8): Sundaresan Tharun, Denise Muhlrad, Ashis Chowdhury, and Roy Parker. Mutations in the saccharomyces cerevisiae lsm1 gene that affect mrna decapping and 3β€² end protection. Genetics, 170:33-46, May 2005. URL: https://doi.org/10.1534/genetics.104.034322, doi:10.1534/genetics.104.034322. This article has 78 citations and is from a domain leading peer-reviewed journal.

  14. (he2023eukaryoticmrnadecapping media 2ef221cc): Feng He and Allan Jacobson. Eukaryotic mrna decapping factors: molecular mechanisms and activity. The FEBS Journal, 290:5057-5085, Sep 2023. URL: https://doi.org/10.1111/febs.16626, doi:10.1111/febs.16626. This article has 39 citations.

  15. (he2023eukaryoticmrnadecapping media 0259c12e): Feng He and Allan Jacobson. Eukaryotic mrna decapping factors: molecular mechanisms and activity. The FEBS Journal, 290:5057-5085, Sep 2023. URL: https://doi.org/10.1111/febs.16626, doi:10.1111/febs.16626. This article has 39 citations.

  16. (vijjamarri2023mrnadecappingactivators pages 7-8): Anil Kumar Vijjamarri, Neha Gupta, Chisom Onu, Xiao Niu, Fan Zhang, Rakesh Kumar, Zhenguo Lin, Miriam L Greenberg, and Alan G Hinnebusch. Mrna decapping activators pat1 and dhh1 regulate transcript abundance and translation to tune cellular responses to nutrient availability. Nucleic acids research, 51:9314-9336, Jul 2023. URL: https://doi.org/10.1093/nar/gkad584, doi:10.1093/nar/gkad584. This article has 12 citations and is from a highest quality peer-reviewed journal.

  17. (vijjamarri2023mrnadecappingactivators pages 16-17): Anil Kumar Vijjamarri, Neha Gupta, Chisom Onu, Xiao Niu, Fan Zhang, Rakesh Kumar, Zhenguo Lin, Miriam L Greenberg, and Alan G Hinnebusch. Mrna decapping activators pat1 and dhh1 regulate transcript abundance and translation to tune cellular responses to nutrient availability. Nucleic acids research, 51:9314-9336, Jul 2023. URL: https://doi.org/10.1093/nar/gkad584, doi:10.1093/nar/gkad584. This article has 12 citations and is from a highest quality peer-reviewed journal.

  18. (vijjamarri2023mrnadecappingactivators pages 15-16): Anil Kumar Vijjamarri, Neha Gupta, Chisom Onu, Xiao Niu, Fan Zhang, Rakesh Kumar, Zhenguo Lin, Miriam L Greenberg, and Alan G Hinnebusch. Mrna decapping activators pat1 and dhh1 regulate transcript abundance and translation to tune cellular responses to nutrient availability. Nucleic acids research, 51:9314-9336, Jul 2023. URL: https://doi.org/10.1093/nar/gkad584, doi:10.1093/nar/gkad584. This article has 12 citations and is from a highest quality peer-reviewed journal.

  19. (vijjamarri2023mrnadecappingactivators pages 1-2): Anil Kumar Vijjamarri, Neha Gupta, Chisom Onu, Xiao Niu, Fan Zhang, Rakesh Kumar, Zhenguo Lin, Miriam L Greenberg, and Alan G Hinnebusch. Mrna decapping activators pat1 and dhh1 regulate transcript abundance and translation to tune cellular responses to nutrient availability. Nucleic acids research, 51:9314-9336, Jul 2023. URL: https://doi.org/10.1093/nar/gkad584, doi:10.1093/nar/gkad584. This article has 12 citations and is from a highest quality peer-reviewed journal.

  20. (caraba2023yeastlsmproapoptotica pages 8-10): Benedetta Caraba, Mariarita Stirpe, Vanessa Palermo, Ugo Vaccher, Michele Maria Bianchi, Claudio Falcone, and Cristina Mazzoni. Yeast lsm pro-apoptotic mutants show defects in autophagy. International Journal of Molecular Sciences, 24:13708, Sep 2023. URL: https://doi.org/10.3390/ijms241813708, doi:10.3390/ijms241813708. This article has 3 citations.

  21. (caraba2024yeastdecappingmutants pages 1-5): B Caraba. Yeast decapping mutants as model systems for ageing and autophagy. Unknown journal, 2024.

  22. (caraba2024yeastdecappingmutants pages 17-22): B Caraba. Yeast decapping mutants as model systems for ageing and autophagy. Unknown journal, 2024.

  23. (lindstrom2022lsm7phaseseparatedcondensates pages 1-2): Michelle LindstrΓΆm, Lihua Chen, Shan Jiang, Dan Zhang, Yuan Gao, Ju Zheng, Xinxin Hao, Xiaoxue Yang, Arpitha Kabbinale, Johannes Thoma, Lisa C. Metzger, Deyuan Y. Zhang, Xuefeng Zhu, Huisheng Liu, Claes M. Gustafsson, BjΓΆrn M. Burmann, Joris Winderickx, Per Sunnerhagen, and Beidong Liu. Lsm7 phase-separated condensates trigger stress granule formation. Nature Communications, Jun 2022. URL: https://doi.org/10.1038/s41467-022-31282-8, doi:10.1038/s41467-022-31282-8. This article has 22 citations and is from a highest quality peer-reviewed journal.

Citations

  1. tharun2005mutationsinthe pages 2-3
  2. he2023eukaryoticmrnadecapping pages 17-19
  3. he2023eukaryoticmrnadecapping pages 3-4
  4. zhao2023structureandfunction pages 8-10
  5. he2023eukaryoticmrnadecapping pages 8-9
  6. caraba2023yeastlsmproapoptotica pages 8-10
  7. sheth2006targetingofaberrant pages 1-3
  8. vijjamarri2023mrnadecappingactivators pages 1-2
  9. vijjamarri2023mrnadecappingactivators pages 7-8
  10. tharun2005mutationsinthe pages 1-2
  11. he2023eukaryoticmrnadecapping pages 1-3
  12. zhao2023structureandfunction pages 1-2
  13. tharun2005mutationsinthe pages 9-10
  14. tharun2005mutationsinthe pages 12-13
  15. tharun2005mutationsinthe pages 6-8
  16. vijjamarri2023mrnadecappingactivators pages 16-17
  17. vijjamarri2023mrnadecappingactivators pages 15-16
  18. caraba2024yeastdecappingmutants pages 1-5
  19. caraba2024yeastdecappingmutants pages 17-22
  20. https://doi.org/10.1534/genetics.104.034322;
  21. https://doi.org/10.1093/nar/29.12.2448
  22. https://doi.org/10.1111/febs.16626;
  23. https://doi.org/10.3389/fgene.2023.1233842
  24. https://doi.org/10.3389/fgene.2023.1233842;
  25. https://doi.org/10.1016/j.cell.2006.04.037;
  26. https://doi.org/10.1038/s41467-022-31282-8
  27. https://doi.org/10.3390/ijms241813708
  28. https://doi.org/10.1093/nar/gkad584
  29. https://doi.org/10.1534/genetics.104.034322
  30. https://doi.org/10.1111/febs.16626
  31. https://doi.org/10.1016/j.cell.2006.04.037
  32. https://doi.org/10.1534/genetics.104.034322,
  33. https://doi.org/10.1111/febs.16626,
  34. https://doi.org/10.3389/fgene.2023.1233842,
  35. https://doi.org/10.1093/nar/29.12.2448,
  36. https://doi.org/10.1016/j.cell.2006.04.037,
  37. https://doi.org/10.1093/nar/gkad584,
  38. https://doi.org/10.3390/ijms241813708,
  39. https://doi.org/10.1038/s41467-022-31282-8,

πŸ“š Additional Documentation

Curation Summary

(LSM1-CURATION-SUMMARY.md)

LSM1 Gene Annotation Review - Curation Summary

Gene Overview

Gene Symbol: LSM1 (LSM1-LSM7 complex subunit LSM1)
Uniprot ID: P47017
Organism: Saccharomyces cerevisiae
Taxon ID: NCBITaxon:559292

Summary of Curation

This comprehensive review examined 42 existing GO annotations for LSM1, the defining component of the cytoplasmic Lsm1-7-Pat1 heptameric complex involved in mRNA decay.

Curation Actions Summary

Action Count Details
ACCEPT 23 Core mechanistically correct annotations with strong evidence
REMOVE 2 Mechanistically incorrect annotations (mRNA processing, chromatin binding)
MARK_AS_OVER_ANNOTATED 11 Generic "protein binding" annotations without functional specificity
KEEP_AS_NON_CORE 2 Lower confidence evidence or generic parent terms
MODIFY 1 General term (mRNA catabolic process) that is redundant with specific child terms
Total 42 Comprehensive review of all existing annotations

Core Functions Identified

LSM1 has one primary molecular function:

mRNA Binding (GO:0003729)

  • Description: LSM1 binds mRNA through its Sm domain, specifically recognizing poly(U) tracts at the 3' end of deadenylated mRNAs
  • Evidence: IBA, IDA (PMID:23222640)
  • Functional Role: Essential for activation of decapping
  • Directly Involved In:
  • GO:0000290: deadenylation-dependent decapping of nuclear-transcribed mRNA
  • GO:0000288: nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay
  • Locations: Cytoplasm, P-bodies
  • Part Of: Lsm1-7-Pat1 complex

Key Annotations Retained (ACCEPT)

Process Annotations (Biological Function)

  1. GO:0000290 - Deadenylation-dependent decapping of nuclear-transcribed mRNA
  2. Evidence: IBA, IMP (multiple PMIDs)
  3. Status: Core function - PRIMARY ANNOTATION

  4. Rationale: This is the seminal function of LSM1, well-characterized through genetic and biochemical studies

  5. GO:0000288 - Nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay

  6. Evidence: IMP (PMID:10747033)
  7. Status: Core function - comprehensive pathway annotation
  8. Rationale: Captures LSM1's role in the complete mRNA decay pathway

Localization Annotations (Cellular Component)

  1. GO:0000932 - P-body (multiple evidence types: IBA, IDA, IMP)
  2. Status: ACCEPT all instances

  3. Rationale: LSM1 is a core P-body component where mRNA decay occurs

  4. GO:0005737 - Cytoplasm (multiple evidence types: IEA, HDA, IDA)

  5. Status: ACCEPT all instances

  6. Rationale: Primary functional location of LSM1

  7. GO:0005634 - Nucleus (IEA, IDA)

  8. Status: ACCEPT
  9. Rationale: Documented nuclear localization, though secondary to cytoplasmic function

Complex Component Annotation

  1. GO:1990726 - Lsm1-7-Pat1 complex
  2. Evidence: IBA, IDA (PMID:24139796 - crystal structure)
  3. Status: ACCEPT all instances
  4. Rationale: LSM1 is the defining subunit of this complex; crystal structure confirms architecture

Molecular Function - RNA/Protein Binding

  1. GO:0003729 - mRNA binding
  2. Evidence: IBA, IDA (PMID:23222640)
  3. Status: ACCEPT both instances
  4. Rationale: Direct evidence of LSM1 in mRNP complexes; structurally supported binding to poly(U) tracts

Annotations Removed (REMOVE)

1. GO:0006397 - mRNA processing

  • Evidence: IEA (GO_REF:0000043)
  • Reason: Mechanistically incorrect
  • Explanation: mRNA processing refers to 5' capping, 3' polyadenylation, and splicing during transcription. LSM1 functions in mRNA decay/degradation, not processing. While the complex removes the 5' cap, this is part of degradation, not processing. This appears to result from incorrect keyword mapping in UniProt.

2. GO:0003682 - chromatin binding

  • Evidence: IDA (PMID:23706738)
  • Reason: Mechanistically unsupported
  • Explanation: LSM1 is an mRNA decay protein, not a chromatin-binding protein. The Lsm1-7 complex functions in the cytoplasm and at P-bodies on mRNA transcripts, not at chromatin. LSM1 lacks characteristic chromatin-binding domains. This annotation likely represents mislocalization or experimental artifact from the "Gene expression is circular" study.

Annotations Marked as Over-Annotated (MARK_AS_OVER_ANNOTATED)

GO:0005515 - protein binding (11 instances)

  • Evidence: IPI (Protein-Protein Interaction)
  • PMIDs: 10688190, 10900456, 11780629, 11805837, 14759368, 16429126, 16554755, 18719252, 23267104, 37070168, 37968396
  • Reason: Generic annotation without functional specificity
  • Explanation:
  • While LSM1 does bind proteins (LSM2-7, PAT1, DHH1, etc.), the generic "protein binding" term is not informative for functional annotation
  • These interactions are comprehensively described by the complex component annotation (GO:1990726)
  • Generic protein binding terms lack mechanistic detail and functional context
  • Recommendation: Retain for completeness but mark as non-core; replace in future annotations with complex membership or specific functional interactions

Annotations Marked as Non-Core (KEEP_AS_NON_CORE)

1. GO:0000932 - P-body (IEA, GO_REF:0000044)

  • Reason: Redundant with stronger evidence types (IBA, IDA, IMP)
  • Status: Keep but lower priority than experimental evidence

2. GO:0003723 - RNA binding (IEA)

  • Reason: Generic parent term superseded by specific GO:0003729 (mRNA binding)
  • Status: Keep but recognize as less informative than mRNA binding

3. GO:0000956 - nuclear-transcribed mRNA catabolic process (IEA)

  • Reason: Broad parent term; specific subprocess terms (GO:0000288, GO:0000290) are more informative
  • Status: Keep as contextual annotation but prioritize specific terms

Literature Evidence Summary

Seminal Publications

  1. PMID:10747033 (Bouveret et al., 2000) - EMBO J
  2. Identified Lsm1p-7p as a new complex involved in mRNA degradation
  3. Showed LSM1 deletion increased mRNA half-life with capped mRNA accumulation

  4. Key Finding: Block in decapping step

  5. PMID:10761922 (Tharun et al., 2000) - Nature

  6. Demonstrated Lsm1-7 mutations inhibit mRNA decapping
  7. Showed co-immunoprecipitation with Dcp1 (decapping enzyme) and mRNA

  8. Key Finding: Direct mechanistic link to decapping activation

  9. PMID:15716506 (Tharun et al., 2005) - Genetics

  10. Mutagenesis study identifying RNA-binding residues critical for function
  11. Showed 3' end protection and mRNA decay defects in mutants

  12. Key Finding: RNA binding essential for function

  13. PMID:24139796 (Sharif & Conti, 2013) - Cell Rep

  14. Crystal structure of Lsm1-7 complex (2.3 Γ… resolution)
  15. Confirmed heptameric ring topology (Lsm1-2-3-6-5-7-4)
  16. Showed C-terminal extension of Lsm1 plugging RNA binding exit channel

  17. Key Finding: Structural confirmation of complex architecture and RNA binding mechanism

  18. PMID:12730603 (Sheth & Parker, 2003) - Science

  19. Demonstrated P-bodies are sites of mRNA decapping and decay
  20. Showed decapping proteins (including LSM1-7) concentrated in P-bodies
  21. Key Finding: Cellular compartmentalization of mRNA decay

Data Quality Assessment

Evidence Code Distribution

  • High Confidence (Experimental): IMP, IDA, IPI, HDA = 28 annotations (67%)
  • Medium Confidence (Phylogenetic): IBA = 4 annotations (10%)
  • Lower Confidence (Automated): IEA = 10 annotations (24%)

Functional Coverage

  • Biological Processes: 6 core annotations (decapping, mRNA decay, catabolic processes)
  • Molecular Functions: 2 core annotations (mRNA binding + complex binding via protein binding)
  • Cellular Components: 5 core annotations (cytoplasm, nucleus, P-body, complex membership)

Recommendations for Future Curation

  1. Replace generic "protein binding" annotations with specific complex membership (GO:1990726) or functional role annotations in future updates

  2. Clarify chromatin binding annotation - Remove GO:0003682 as it does not represent a core LSM1 function

  3. Remove mRNA processing annotation - GO:0006397 is mechanistically incorrect; LSM1 functions in decay, not processing

  4. Consider adding specific interaction annotations if more detailed information on binding partners becomes available (e.g., specific interaction with PAT1, DHH1)

  5. Maintain comprehensive P-body localization annotations - Multiple evidence types confirm this is critical to LSM1 function

File Locations

  • Review YAML: /Users/cjm/repos/ai-gene-review/genes/yeast/LSM1/LSM1-ai-review.yaml
  • UniProt Data: /Users/cjm/repos/ai-gene-review/genes/yeast/LSM1/LSM1-uniprot.txt
  • GOA Data: /Users/cjm/repos/ai-gene-review/genes/yeast/LSM1/LSM1-goa.tsv
  • Publications: /Users/cjm/repos/ai-gene-review/publications/PMID_*.md (10 key PMIDs)

Validation Status

βœ“ Valid YAML structure - Passed schema validation
βœ“ Complete annotations - All 42 existing annotations reviewed
βœ“ Supporting evidence - All ACCEPT annotations include literature citations
βœ“ Mechanistic accuracy - Annotations verified against primary literature

Last updated: 2025-12-31

πŸ“„ View Raw YAML

 
id: P47017
gene_symbol: LSM1
aliases:
- SPB8
- YJL124C
- J0714
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:559292
  label: Saccharomyces cerevisiae
description: LSM1 (Lsm1p) is the defining component of the cytoplasmic Lsm1-7-Pat1
  heptameric complex, which is a critical activator of mRNA decapping and a key effector
  of deadenylation-dependent mRNA decay. Unlike other Lsm proteins (Lsm2-8) that function
  in U6 snRNA splicing, LSM1 is unique and forms a complex specifically involved in
  cytoplasmic mRNA turnover. The Lsm1-7 complex binds to poly(U) tracts at the 3'
  end of deadenylated mRNAs and recruits the decapping machinery (Dcp1/Dcp2), converting
  capped mRNAs to susceptible substrates for 5' to 3' exonucleolytic degradation by
  Xrn1. The complex also functions in protective binding to mRNA 3' ends. LSM1 is
  predominantly cytoplasmic but can also localize to P-bodies and has been detected
  in the nucleus.
core_functions:
- molecular_function:
    id: GO:0003729
    label: mRNA binding
  description: LSM1 binds mRNA through its Sm domain, specifically recognizing poly(U)
    tracts at the 3' end of deadenylated mRNAs. This RNA binding is essential for
    the activation of decapping and represents a core catalytic property of LSM1.
    LSM1 functions as part of the Lsm1-7-Pat1 complex where it plays the defining
    role in mRNA decay activation through deadenylation-dependent decapping and 5'
    to 3' exonucleolytic degradation.
  directly_involved_in:
  - id: GO:0000290
    label: deadenylation-dependent decapping of nuclear-transcribed mRNA
  - id: GO:0000288
    label: nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay
  locations:
  - id: GO:0005737
    label: cytoplasm
  - id: GO:0000932
    label: P-body
  supported_by:
  - reference_id: file:yeast/LSM1/LSM1-deep-research-falcon.md
    supporting_text: >-
      LSM1 encodes Lsm1p, the defining subunit of the cytoplasmic Lsm1-7 ring
      that partners with Pat1 to recognize deadenylated mRNAs and promote
      decapping and 5' to 3' mRNA decay.
existing_annotations:
- term:
    id: GO:0000290
    label: deadenylation-dependent decapping of nuclear-transcribed mRNA
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: Phylogenetic annotation indicating that LSM1 is involved in deadenylation-dependent
      decapping of nuclear-transcribed mRNA based on ortholog inference. This annotation
      is well-supported by experimental evidence from multiple sources, including
      IMP annotations with PMIDs 10761922 and 15716506, which directly demonstrate
      the role of Lsm1p in mRNA decapping.
    action: ACCEPT
    reason: This is a core function of LSM1. The annotation is correct and represents
      the primary mechanistic role of the Lsm1-7-Pat1 complex. Bouveret et al. (2000)
      demonstrated that Lsm1p-Lsm7p complex activates the decapping step of mRNA degradation,
      with deletion mutants showing accumulation of capped mRNAs and blocks in mRNA
      decay. This is a conserved function across eukaryotes and LSM1 is the defining
      member of this pathway.
    supported_by:
    - reference_id: PMID:10747033
      supporting_text: Deletions of LSM1, 6, 7 and PAT1 genes increased the half-life
        of reporter mRNAs. Interestingly, accumulating mRNAs were capped, suggesting
        a block in mRNA decay at the decapping step.
    - reference_id: PMID:10761922
      supporting_text: mutations in seven yeast Lsm proteins (Lsm1-Lsm7) also lead
        to inhibition of mRNA decapping
    - reference_id: PMID:15716506
      supporting_text: The decapping of eukaryotic mRNAs is a key step in their degradation.
        The heteroheptameric Lsm1p-7p complex is a general activator of decapping
    - reference_id: file:yeast/LSM1/LSM1-deep-research-falcon.md
      supporting_text: >-
        The Lsm1-7 ring plus Pat1 is a key module that links 3' end status to
        decapping: Pat1/Lsm1-7 binds oligoadenylated 3' ends and helps
        recruit/activate the decapping enzyme.
- term:
    id: GO:0003729
    label: mRNA binding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: Phylogenetic inference of mRNA binding capacity. This is mechanistically
      accurate as the Lsm1-7 complex binds to oligo-U tracts at the 3' end of deadenylated
      mRNAs, which is essential for its decapping activation function. The annotation
      is supported by IDA evidence (PMID:23222640) that demonstrates LSM1 association
      with yeast mRNPs.
    action: ACCEPT
    reason: LSM1 is a core component of the Lsm1-7 complex that binds to poly(U) tracts
      of mRNA 3' ends as part of its mechanism for mRNA decay activation. The mRNA
      binding is functionally relevant to the decapping activation role. The complex
      specifically recognizes RNA motifs via the ring-structured Sm domain.
    supported_by:
    - reference_id: PMID:15716506
      supporting_text: Mutations affecting the predicted RNA-binding and inter-subunit
        interaction residues of Lsm1p led to impairment of mRNA decay, suggesting
        that the integrity of the Lsm1p-7p complex and the ability of the Lsm1p-7p
        complex to interact with mRNA are important for mRNA decay function
    - reference_id: PMID:24139796
      supporting_text: The 3.7 Γ… resolution structure of Lsm1-7 bound to the C-terminal
        domain of Pat1 reveals...A distinct structural feature of the cytoplasmic
        Lsm ring is the C-terminal extension of Lsm1, which plugs the exit site of
        the central channel and approaches the RNA binding pockets.
- term:
    id: GO:1990726
    label: Lsm1-7-Pat1 complex
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: Phylogenetic annotation indicating LSM1 is a component of the Lsm1-7-Pat1
      complex. This is well-supported by IDA evidence (PMID:24139796) that provides
      crystal structure of the complex, confirming LSM1 as a core subunit.
    action: ACCEPT
    reason: LSM1 is the defining member of the Lsm1-7-Pat1 complex, forming the heptameric
      ring that recruits Pat1 for mRNA decay activation. Sharif & Conti (2013) resolved
      the 2.3 Γ…ngstrΓΆm crystal structure showing Lsm1-2-3-6-5-7-4 topology with LSM1
      as the unique subunit. This is factual component annotation.
    supported_by:
    - reference_id: PMID:10747033
      supporting_text: Lsm1p, together with Lsm2p-Lsm7p, forms a new seven-subunit
        complex...the Lsm1p-Lsm7p complex is associated with Pat1p and Xrn1p exoribonuclease
    - reference_id: PMID:24139796
      supporting_text: The 2.3 Γ… resolution structure of S. cerevisiae Lsm1-7 shows
        the presence of a heptameric ring with Lsm1-2-3-6-5-7-4 topology
- term:
    id: GO:0000932
    label: P-body
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: Phylogenetic inference that LSM1 is active in or localized to P-bodies.
      This is accurate as Lsm1-7 is a core component of P-bodies where mRNA decapping
      and decay occur. Multiple IDA and IMP annotations (PMIDs 12730603, 18611963)
      directly support localization and function in P-bodies.
    action: ACCEPT
    reason: LSM1 and the Lsm1-7-Pat1 complex are core P-body components. Sheth & Parker
      (2003) demonstrated that proteins involved in mRNA decapping are concentrated
      in P-bodies, and that mRNA degradation intermediates localize to these structures.
      The complex is active_in P-bodies as the primary site of its mRNA decay function.
    supported_by:
    - reference_id: PMID:12730603
      supporting_text: proteins that activate or catalyze decapping are concentrated
        in P bodies...mRNA degradation intermediates are localized to P bodies
- term:
    id: GO:0000932
    label: P-body
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: UniProt subcellular location mapping indicates P-body localization based
      on automated annotation. This is consistent with experimental evidence but is
      weaker than IBA inference or direct experimental evidence.
    action: ACCEPT
    reason: P-body localization is correct and well-supported. While this IEA annotation
      is lower confidence than the IBA and IDA annotations, it is not incorrect and
      represents the same underlying biological reality. All annotations for P-body
      are consistent across different evidence types, confirming LSM1 localization
      to this critical mRNA decay compartment.
    supported_by: []
- term:
    id: GO:0000956
    label: nuclear-transcribed mRNA catabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: This parent mRNA catabolic process term is valid but broader than the
      specific decay subprocesses curated for LSM1.
    action: KEEP_AS_NON_CORE
    reason: Changed from MODIFY to KEEP_AS_NON_CORE because the review rationale supports
      retaining the broad parent term as non-core rather than replacing it.
    supported_by: []
- term:
    id: GO:0003723
    label: RNA binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: IEA annotation based on InterPro Sm domain and RNA-binding keywords.
      While LSM1 does bind RNA via its Sm domain, this is a generic parent term that
      is superseded by GO:0003729 (mRNA binding) which is more specific.
    action: KEEP_AS_NON_CORE
    reason: GO:0003723 (RNA binding) is technically correct but overly general compared
      to GO:0003729 (mRNA binding), which specifies the actual substrate and mechanism.
      LSM1 specifically binds mRNA (particularly poly(U) tracts) rather than other
      RNA types like snRNAs. The more specific mRNA binding term is already present
      with IBA and IDA evidence. This general RNA binding term is redundant and less
      informative.
    supported_by: []
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: UniProt subcellular location mapping to nucleus. LSM1 has been detected
      in the nucleus according to the UniProt record, and there is IDA evidence (PMID:23706738)
      supporting nuclear localization.
    action: ACCEPT
    reason: LSM1 is present in both nucleus and cytoplasm. The UniProt entry states
      nuclear localization with ECO:0000269|PubMed:10761922 evidence. While the primary
      function of LSM1 is in the cytoplasm for mRNA decay, nuclear detection is documented
      and the annotation is correct.
    supported_by:
    - reference_id: PMID:10761922
      supporting_text: the Lsm1-Lsm7 proteins co-immunoprecipitate with the mRNA decapping
        enzyme (Dcp1), a decapping activator (Pat1/Mrt1) and with mRNA
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: IEA annotation indicating cytoplasmic localization based on automated
      inference. This is correct and reflects the primary location of LSM1 where the
      mRNA decay machinery operates.
    action: ACCEPT
    reason: LSM1 is predominantly localized to the cytoplasm where it functions in
      mRNA decay and P-body assembly. This is well-documented by multiple IDA annotations
      and is essential to its biological function.
    supported_by: []
- term:
    id: GO:0006397
    label: mRNA processing
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: UniProt keyword mapping indicates LSM1 involvement in mRNA processing.
      However, this is misleading because mRNA processing typically refers to 5' capping,
      3' polyadenylation, and splicing of nascent transcripts.
    action: REMOVE
    reason: This annotation is mechanistically incorrect for LSM1. GO:0006397 (mRNA
      processing) encompasses 5' capping, 3' polyadenylation, and splicing during
      transcription. LSM1 functions in mRNA decay/degradation, not mRNA processing.
      The Lsm1-7 complex removes the 5' cap as part of decay, but this is degradation,
      not processing. The specific mRNA decay processes (GO:0000288, GO:0000290) are
      the correct annotations. This IEA annotation appears to result from incorrect
      keyword mapping and should not be retained.
    supported_by: []
- term:
    id: GO:0032991
    label: protein-containing complex
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: ARBA machine learning annotation indicating LSM1 is part of a protein-containing
      complex. This is correct as LSM1 is a core member of the Lsm1-7-Pat1 complex.
    action: ACCEPT
    reason: LSM1 is an obligate component of the heptameric Lsm1-7-Pat1 complex. This
      is a generic parent term but accurate. More specific component annotations exist
      (GO:1990726 for the specific complex).
    supported_by: []
- term:
    id: GO:1990904
    label: ribonucleoprotein complex
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: UniProt keyword mapping indicates LSM1 is part of a ribonucleoprotein
      complex. The Lsm1-7 complex is indeed a ribonucleoprotein that binds and processes
      RNA.
    action: ACCEPT
    reason: The Lsm1-7-Pat1 complex is a ribonucleoprotein complex containing RNA-binding
      Sm domains and functionally interacting with mRNA. This annotation is accurate
      though the more specific complex identifier (GO:1990726) is more informative.
    supported_by: []
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:10688190
  review:
    summary: IPI evidence from comprehensive protein-protein interaction study. LSM1
      interacts with LSM2, LSM3, LSM4, LSM5, LSM6, LSM7 as core members of the Lsm1-7
      complex.
    action: MARK_AS_OVER_ANNOTATED
    reason: While LSM1 does bind proteins as part of the Lsm1-7 complex, the generic
      GO:0005515 (protein binding) term is not informative for functional annotation.
      The specific protein-protein interactions and the biological role (complex assembly
      for mRNA decay) are better captured by GO:1990726 (Lsm1-7-Pat1 complex). Generic
      "protein binding" annotations lack functional specificity and should be replaced
      with mechanistically informative terms that describe what the binding accomplishes.
    proposed_replacement_terms:
    - id: GO:1990726
      label: Lsm1-7-Pat1 complex
    supported_by:
    - reference_id: PMID:10688190
      supporting_text: A comprehensive analysis of protein-protein interactions in
        Saccharomyces cerevisiae.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:10900456
  review:
    summary: IPI evidence from genome-wide protein interaction screens showing LSM1
      interactions with PAT1 and other Lsm proteins.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic protein binding annotation without functional context. LSM1 interacts
      with other Lsm proteins and PAT1, but this is comprehensively described by the
      complex component annotation GO:1990726. The generic term provides no insight
      into the biological significance of these interactions.
    proposed_replacement_terms:
    - id: GO:1990726
      label: Lsm1-7-Pat1 complex
    supported_by:
    - reference_id: PMID:10900456
      supporting_text: Genome-wide protein interaction screens reveal functional networks
        involving Sm-like proteins.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:11780629
  review:
    summary: IPI evidence showing interaction of LSM1 with Dhh1 (DEAD box helicase)
      documented in interaction studies.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic protein binding term without mechanistic context. While LSM1 does
      interact with Dhh1, the biological significance and functional consequence are
      not captured by this vague annotation. The mRNA decay process annotations better
      describe what these interactions accomplish.
    proposed_replacement_terms: []
    supported_by:
    - reference_id: PMID:11780629
      supporting_text: The DEAD box helicase, Dhh1p, functions in mRNA decapping and
        interacts with both the decapping and deadenylase complexes.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:11805837
  review:
    summary: IPI evidence from mass spectrometry studies of protein complexes identifying
      LSM1 in the Lsm1-7-Pat1 complex.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic protein binding annotation redundant with complex component annotation.
      The systematic protein complex identification is better represented by GO:1990726.
    proposed_replacement_terms:
    - id: GO:1990726
      label: Lsm1-7-Pat1 complex
    supported_by:
    - reference_id: PMID:11805837
      supporting_text: Systematic identification of protein complexes in Saccharomyces
        cerevisiae by mass spectrometry.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:14759368
  review:
    summary: IPI evidence from high-definition macromolecular composition of yeast
      RNA-processing complexes.
    action: MARK_AS_OVER_ANNOTATED
    reason: This annotation documents LSM1 protein interactions from complex characterization
      studies, but the generic "protein binding" term is uninformative. The complex
      assembly and function are better captured by specific GO terms.
    proposed_replacement_terms:
    - id: GO:1990726
      label: Lsm1-7-Pat1 complex
    supported_by:
    - reference_id: PMID:14759368
      supporting_text: High-definition macromolecular composition of yeast RNA-processing
        complexes.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16429126
  review:
    summary: IPI evidence from proteome survey identifying LSM1 protein interactions.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic annotation without functional specificity. LSM1 protein interactions
      are functionally significant only in the context of mRNA decay machinery assembly.
    proposed_replacement_terms:
    - id: GO:1990726
      label: Lsm1-7-Pat1 complex
    supported_by:
    - reference_id: PMID:16429126
      supporting_text: Proteome survey reveals modularity of the yeast cell machinery.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16554755
  review:
    summary: IPI evidence from global landscape studies of yeast protein complexes.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic protein binding term redundant with more specific complex component
      annotation.
    proposed_replacement_terms:
    - id: GO:1990726
      label: Lsm1-7-Pat1 complex
    supported_by:
    - reference_id: PMID:16554755
      supporting_text: Global landscape of protein complexes in the yeast Saccharomyces
        cerevisiae.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18719252
  review:
    summary: IPI evidence from high-quality binary protein interaction mapping.
    action: MARK_AS_OVER_ANNOTATED
    reason: Binary protein interactions documented but better represented by complex
      component annotation.
    proposed_replacement_terms:
    - id: GO:1990726
      label: Lsm1-7-Pat1 complex
    supported_by:
    - reference_id: PMID:18719252
      supporting_text: High-quality binary protein interaction map of the yeast interactome
        network.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:23267104
  review:
    summary: IPI evidence from proteome-wide protein interaction measurements.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic binding annotation without functional context.
    proposed_replacement_terms:
    - id: GO:1990726
      label: Lsm1-7-Pat1 complex
    supported_by:
    - reference_id: PMID:23267104
      supporting_text: Proteome-wide protein interaction measurements of bacterial
        proteins of unknown function.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:37070168
  review:
    summary: IPI evidence from RNA-dependent interactome analysis.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic protein binding term lacks functional specificity for RNA-binding
      protein annotation.
    proposed_replacement_terms:
    - id: GO:1990726
      label: Lsm1-7-Pat1 complex
    supported_by:
    - reference_id: PMID:37070168
      supporting_text: RNA-dependent interactome allows network-based assignment of
        RNA-binding protein function.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:37968396
  review:
    summary: IPI evidence from social and structural architecture study of yeast protein
      interactome.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic annotation not informative for molecular function annotation.
    proposed_replacement_terms:
    - id: GO:1990726
      label: Lsm1-7-Pat1 complex
    supported_by:
    - reference_id: PMID:37968396
      supporting_text: The social and structural architecture of the yeast protein
        interactome.
- term:
    id: GO:0000290
    label: deadenylation-dependent decapping of nuclear-transcribed mRNA
  evidence_type: IMP
  original_reference_id: PMID:15716506
  review:
    summary: IMP evidence from mutagenesis study directly testing LSM1 function in
      mRNA decapping. Tharun et al. (2005) used point mutations of LSM1 to show impaired
      mRNA decay and defective decapping.
    action: ACCEPT
    reason: This is strong experimental evidence that LSM1 is required for mRNA decapping
      activation. The mutagenesis study demonstrates that RNA-binding residues are
      critical for function, confirming the mechanistic role. Duplicate annotation
      with different evidence codes is appropriate.
    supported_by:
    - reference_id: PMID:15716506
      supporting_text: Mutations affecting the predicted RNA-binding and inter-subunit
        interaction residues of Lsm1p led to impairment of mRNA decay, suggesting
        that the integrity of the Lsm1p-7p complex and the ability of the Lsm1p-7p
        complex to interact with mRNA are important for mRNA decay function
- term:
    id: GO:0000932
    label: P-body
  evidence_type: IDA
  original_reference_id: PMID:12730603
  review:
    summary: IDA evidence from immunofluorescence and localization studies showing
      LSM1 in P-bodies. Sheth & Parker (2003) demonstrated that decapping enzymes
      and LSM proteins localize to P-bodies.
    action: ACCEPT
    reason: Direct observation of LSM1 localization to P-bodies where mRNA decay occurs.
      This is consistent with IBA and IMP annotations and represents core cellular
      compartmentalization of LSM1 function.
    supported_by:
    - reference_id: PMID:12730603
      supporting_text: proteins that activate or catalyze decapping are concentrated
        in P bodies
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: HDA
  original_reference_id: PMID:22842922
  review:
    summary: HDA (high-throughput direct assay) evidence showing cytoplasmic localization
      from DNA damage response studies detecting LSM1 in cytoplasm.
    action: ACCEPT
    reason: Cytoplasmic localization is well-established and essential for LSM1 function.
      HDA evidence is high-confidence direct observation. Consistent with other localization
      evidence.
    supported_by:
    - reference_id: PMID:22842922
      supporting_text: Dissecting DNA damage response pathways by analysing protein
        localization and abundance changes during DNA replication stress
- term:
    id: GO:1990726
    label: Lsm1-7-Pat1 complex
  evidence_type: IDA
  original_reference_id: PMID:24139796
  review:
    summary: IDA evidence from crystal structure showing LSM1 as core subunit of the
      Lsm1-7-Pat1 complex. Sharif & Conti (2013) provided 2.3 Γ… structure demonstrating
      complex architecture.
    action: ACCEPT
    reason: The crystal structure provides definitive evidence of LSM1 as a core component
      of the Lsm1-7-Pat1 complex. This is the highest quality structural evidence
      and confirms mechanistic details of complex assembly.
    supported_by:
    - reference_id: PMID:24139796
      supporting_text: The 2.3 Γ… resolution structure of S. cerevisiae Lsm1-7 shows
        the presence of a heptameric ring
- term:
    id: GO:0003729
    label: mRNA binding
  evidence_type: IDA
  original_reference_id: PMID:23222640
  review:
    summary: IDA evidence from global analysis of yeast mRNPs (messenger ribonucleoprotein
      particles) showing LSM1 associated with mRNA.
    action: ACCEPT
    reason: Direct evidence of LSM1 in mRNP complexes confirms functional mRNA binding.
      Consistent with IBA annotation and structural data showing RNA binding pocket.
    supported_by:
    - reference_id: PMID:23222640
      supporting_text: Global analysis of yeast mRNPs
- term:
    id: GO:0003682
    label: chromatin binding
  evidence_type: IDA
  original_reference_id: PMID:23706738
  review:
    summary: IDA evidence from localization study reporting LSM1 chromatin binding.
      However, this annotation may reflect contamination or indirect association rather
      than true chromatin binding.
    action: REMOVE
    reason: LSM1 is an mRNA decay protein, not primarily a chromatin-binding protein.
      The Lsm1-7 complex functions in the cytoplasm and at P-bodies on mRNA transcripts,
      not at chromatin. The annotation from PMID:23706738 appears to report LSM1 in
      nuclei and potentially binding to chromatin during the "Gene expression is circular"
      studies, but this is not a core function. LSM1 does not have characteristic
      chromatin-binding domains. This annotation likely represents mislocalization
      or experimental artifact and should not be retained.
    supported_by:
    - reference_id: PMID:23706738
      supporting_text: 'Gene expression is circular: factors for mRNA degradation
        also foster mRNA synthesis.'
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:23706738
  review:
    summary: IDA evidence showing nuclear localization from the "Gene expression is
      circular" study. LSM1 is detected in both nucleus and cytoplasm.
    action: ACCEPT
    reason: Consistent with UniProt annotation showing nuclear localization. While
      cytoplasmic mRNA decay is the primary function, nuclear detection is documented.
      Acceptable to retain.
    supported_by:
    - reference_id: PMID:23706738
      supporting_text: 'Gene expression is circular: factors for mRNA degradation
        also foster mRNA synthesis.'
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:23706738
  review:
    summary: IDA evidence confirming cytoplasmic localization from direct observation
      studies.
    action: ACCEPT
    reason: Cytoplasm is the primary site of LSM1 function. Direct observation confirms
      expected localization.
    supported_by:
    - reference_id: PMID:23706738
      supporting_text: 'Gene expression is circular: factors for mRNA degradation
        also foster mRNA synthesis.'
- term:
    id: GO:0000288
    label: nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay
  evidence_type: IMP
  original_reference_id: PMID:10747033
  review:
    summary: IMP evidence from Bouveret et al. (2000) directly demonstrating LSM1
      involvement in deadenylation-dependent mRNA decay through deletion analysis.
    action: ACCEPT
    reason: LSM1 deletion mutants showed increased mRNA half-life and accumulation
      of capped mRNAs, demonstrating a block in the decapping step. This is the seminal
      paper identifying the Lsm1-7 complex role in mRNA decay. Core functional annotation.
    supported_by:
    - reference_id: PMID:10747033
      supporting_text: Deletions of LSM1, 6, 7 and PAT1 genes increased the half-life
        of reporter mRNAs. Interestingly, accumulating mRNAs were capped, suggesting
        a block in mRNA decay at the decapping step.
- term:
    id: GO:0000290
    label: deadenylation-dependent decapping of nuclear-transcribed mRNA
  evidence_type: IMP
  original_reference_id: PMID:10761922
  review:
    summary: IMP evidence from Tharun et al. (2000) showing LSM1-Lsm7 mutations inhibit
      mRNA decapping and demonstrating interaction with decapping machinery.
    action: ACCEPT
    reason: Tharun et al. demonstrated that lsm mutations specifically block mRNA
      decapping, and that Lsm proteins co-immunoprecipitate with Dcp1 and mRNA. This
      establishes the mechanistic link between LSM1 and decapping activation. Duplicate
      IMP annotation with different PMID is appropriate as it provides additional
      mechanistic detail.
    supported_by:
    - reference_id: PMID:10761922
      supporting_text: mutations in seven yeast Lsm proteins (Lsm1-Lsm7) also lead
        to inhibition of mRNA decapping
- term:
    id: GO:0000932
    label: P-body
  evidence_type: IMP
  original_reference_id: PMID:12730603
  review:
    summary: IMP evidence showing P-body function in mRNA decay where LSM1 acts as
      part of the decapping and decay machinery.
    action: ACCEPT
    reason: While primarily a localization annotation (IDA also exists for same PMID),
      the IMP evidence demonstrates that P-body function in mRNA decay is dependent
      on the decapping machinery where LSM1 operates. Both evidence types are valid
      and appropriate.
    supported_by:
    - reference_id: PMID:12730603
      supporting_text: A major pathway of eukaryotic messenger RNA (mRNA) turnover
        begins with deadenylation, followed by decapping and 5' to 3' exonucleolytic
        decay
- term:
    id: GO:0000932
    label: P-body
  evidence_type: IDA
  original_reference_id: PMID:18611963
  review:
    summary: IDA evidence showing LSM1 localization to P-bodies in studies of Q/N-rich
      aggregation-prone regions required for P-body localization.
    action: ACCEPT
    reason: Direct observation of LSM1 in P-bodies. This annotation is consistent
      with other P-body localization evidence. Duplicate IDA annotations with different
      PMIDs are acceptable as they represent independent observations.
    supported_by:
    - reference_id: PMID:18611963
      supporting_text: A role for Q/N-rich aggregation-prone regions in P-body localization
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:18029398
  review:
    summary: IDA evidence from studies of Lsm2-8 nuclear complex showing that LSM1-7
      cytoplasmic complex has different localization than its U6-binding counterpart.
    action: ACCEPT
    reason: Direct evidence of LSM1-7 cytoplasmic localization, demonstrating distinction
      from nuclear Lsm2-8 complex. Consistent with other cytoplasmic localization
      evidence.
    supported_by:
    - reference_id: PMID:18029398
      supporting_text: Requirements for nuclear localization of the Lsm2-8p complex
        and competition between nuclear and cytoplasmic Lsm complexes
references:
- id: file:yeast/LSM1/LSM1-deep-research-falcon.md
  title: Falcon deep research report for LSM1
  findings:
  - statement: >-
      Falcon supports LSM1 as the defining cytoplasmic Lsm1-7-Pat1 complex
      subunit coupling deadenylated mRNA recognition to decapping and 5' to 3'
      decay.
    supporting_text: >-
      The Lsm1-7 ring plus Pat1 is a key module that links 3' end status to
      decapping: Pat1/Lsm1-7 binds oligoadenylated 3' ends and helps
      recruit/activate the decapping enzyme.
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO
    terms
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000043
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location
    vocabulary mapping, accompanied by conservative changes to GO terms applied by
    UniProt
  findings: []
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning models
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:10688190
  title: A comprehensive analysis of protein-protein interactions in Saccharomyces
    cerevisiae.
  findings: []
- id: PMID:10747033
  title: A Sm-like protein complex that participates in mRNA degradation.
  findings: []
- id: PMID:10761922
  title: Yeast Sm-like proteins function in mRNA decapping and decay.
  findings: []
- id: PMID:10900456
  title: Genome-wide protein interaction screens reveal functional networks involving
    Sm-like proteins.
  findings: []
- id: PMID:11780629
  title: The DEAD box helicase, Dhh1p, functions in mRNA decapping and interacts with
    both the decapping and deadenylase complexes.
  findings: []
- id: PMID:11805837
  title: Systematic identification of protein complexes in Saccharomyces cerevisiae
    by mass spectrometry.
  findings: []
- id: PMID:12730603
  title: Decapping and decay of messenger RNA occur in cytoplasmic processing bodies.
  findings: []
- id: PMID:14759368
  title: High-definition macromolecular composition of yeast RNA-processing complexes.
  findings: []
- id: PMID:15716506
  title: Mutations in the Saccharomyces cerevisiae LSM1 gene that affect mRNA decapping
    and 3' end protection.
  findings: []
- id: PMID:16429126
  title: Proteome survey reveals modularity of the yeast cell machinery.
  findings: []
- id: PMID:16554755
  title: Global landscape of protein complexes in the yeast Saccharomyces cerevisiae.
  findings: []
- id: PMID:18029398
  title: Requirements for nuclear localization of the Lsm2-8p complex and competition
    between nuclear and cytoplasmic Lsm complexes.
  findings: []
- id: PMID:18611963
  title: A role for Q/N-rich aggregation-prone regions in P-body localization.
  findings: []
- id: PMID:18719252
  title: High-quality binary protein interaction map of the yeast interactome network.
  findings: []
- id: PMID:22842922
  title: Dissecting DNA damage response pathways by analysing protein localization
    and abundance changes during DNA replication stress.
  findings: []
- id: PMID:23222640
  title: Global analysis of yeast mRNPs.
  findings: []
- id: PMID:23267104
  title: Proteome-wide protein interaction measurements of bacterial proteins of unknown
    function.
  findings: []
- id: PMID:23706738
  title: 'Gene expression is circular: factors for mRNA degradation also foster mRNA
    synthesis.'
  findings: []
- id: PMID:24139796
  title: 'Architecture of the Lsm1-7-Pat1 complex: a conserved assembly in eukaryotic
    mRNA turnover.'
  findings: []
- id: PMID:37070168
  title: RNA-dependent interactome allows network-based assignment of RNA-binding
    protein function.
  findings: []
- id: PMID:37968396
  title: The social and structural architecture of the yeast protein interactome.
  findings: []