CSDE1

UniProt ID: O75534
Organism: Homo sapiens
Review Status: DRAFT
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Gene Description

CSDE1 (UNR) is a cytoplasmic RNA-binding protein with multiple cold-shock domains that coordinates RNA with regulatory protein partners. It modulates translation and mRNA stability through transcript- and ribonucleoprotein-specific interactions, including the c-FOS coding-region determinant/poly(A)-binding-protein assembly, internal ribosome entry sites, and miRNA-induced silencing complexes. Its effects on stabilization and turnover depend on translation and complex state. CSDE1 also associates with stress granules and selected lncRNAs in defined cellular contexts. Alternative splicing changes N-terminal and internal protein sequences.

Existing Annotations Review

GO Term Evidence Action Reason
IEA
GO_REF:0000044
UNDECIDED
Summary: The P-body mapping is traceable, but target localization remains unresolved.
Reason: The current SL-0230 mapping correctly denotes GO:0000932. UniProt cites PMID:32354837 for CSDE1 localization, but the inspected original main text and supplementary construct/IF methods and captions chiefly localize 4E-T and its mutants; the relevant 4E-T deletion removes UNR binding. PMID:27342281 reports absence of UNR/unrip from P-bodies in its studied context. Neither that conditional negative nor failure to locate a direct CSDE1 assay establishes universal exclusion. Retain the original assertion pending resolution of its specific localization evidence.
Propagation Review
Root cause: UNRESOLVED
Sources checked:
UniProtKB-SubCell:SL-0230 UNRESOLVED
The vocabulary-to-GO mapping is exact; the underlying target-specific experimental localization remains unresolved.
GO:0003676 nucleic acid binding
IEA
GO_REF:0000002
MODIFY
Summary: Refine nucleic-acid binding to the demonstrated RNA-binding activity.
Reason: InterPro nucleic-acid binding is compatible with the established activity but RNA binding is the supported informative scope, including both mRNA and lncRNA; do not claim absence of all DNA binding from this refinement.
Propagation Review
Root cause: NO FAILURE CORE
Sources checked:
InterPro:IPR002059 SUPPORTS TRANSFER
Actual target domain membership and broad nucleic-acid-binding mapping are sound; direct RNA experiments justify greater target precision.
InterPro:IPR011129 SUPPORTS TRANSFER
Actual target domain membership and broad nucleic-acid-binding mapping are sound; direct RNA experiments justify greater target precision.
Proposed replacements: RNA binding
GO:0003723 RNA binding
HDA
PMID:22658674
Insights into RNA biology from an atlas of mammalian mRNA-bi...
MODIFY
Summary: Refine the supported RNA association to mRNA binding.
Reason: The original HeLa study used UV crosslinking and stringent oligo(dT) capture. Its original supplementary workbook lists CSDE1/ENSG00000009307 in the mRNA interactome (row 11), including CL and control detection and significant enrichment; control detection is not misrepresented as absence. GO:0003729 is the verified mRNA-binding child of RNA binding and agrees with direct CSDE1 mRNA studies. This is ligand precision, not rejection of the positive screen.
Proposed replacements: mRNA binding
GO:0003723 RNA binding
HDA
PMID:22681889
The mRNA-bound proteome and its global occupancy profile on ...
MODIFY
Summary: Refine the supported RNA association to mRNA binding.
Reason: The complete abstract describes photoreactive UV crosslinking and oligo(dT) isolation of the mRNA-bound proteome from a human embryonic kidney cell line. The target-specific supplementary row and complete Methods were not personally recovered, so the existing curator assignment is retained rather than independently re-created. GO:0003729 is the verified mRNA-binding child of RNA binding and agrees with direct CSDE1 mRNA studies. This is ligand precision, not rejection of the positive screen.
Proposed replacements: mRNA binding
GO:0003729 mRNA binding
TAS
PMID:36354136
N(6) -methyladenosine-modified lncRNA ARHGAP5-AS1 stabilises...
ACCEPT
Summary: Retain the established mRNA-binding function with the TAS source scope explicit.
Reason: Retain the TAS mRNA-binding assertion. The HCC paper introduces this known function; its own direct RNA experiments concern ARHGAP5-AS1. Independent mCRD and IRES assays establish mRNA binding without converting the TAS source into an IDA experiment.
Supporting Evidence:
PMID:36354136
CSDE1 is an RNA‐binding protein and coordinates oncogenic RNA regulons
GO:0005515 protein binding
IPI
PMID:25416956
A proteome-scale map of the human interactome network.
KEEP AS NON CORE
Summary: Retain the positive CSDE1–HID1 binary interaction at the screen-assay scope.
Reason: PMID:25416956 and three exact IntAct records support the CSDE1/O75534–HID1/Q8IV36 pair in two-hybrid pooling, array and validated assay records. The reference participant sequences independently reproduce their ROGIDs. The paper describes repeat testing and identity confirmation; orthogonal validation is dataset-level and is not attributed to this pair. HID1 secretory-vesicle biology does not by itself establish a more specific molecular binding class or a CSDE1 secretory function. Supported generic binding is retained as non-core under the standing campaign policy, without requiring native-compartment coincidence.
GO:0005515 protein binding
IPI
PMID:25416956
A proteome-scale map of the human interactome network.
KEEP AS NON CORE
Summary: Retain the positive CSDE1–FAM9B binary interaction at the screen-assay scope.
Reason: Three exact PMID:25416956 IntAct records identify CSDE1/O75534 and FAM9B/Q8IZU0, with independently reconstructed reference-sequence ROGIDs. FAM9B identity and its contextual annotations do not supply a defensible specific molecular partner class. The positive pair is retained as non-core under the standing generic-binding policy; no germ-cell or meiotic function is assigned to CSDE1 from this interaction.
GO:0005515 protein binding
IPI
PMID:27342281
The DDX6-4E-T interaction mediates translational repression ...
KEEP AS NON CORE
Summary: Retain the experimentally supported UNR–4E-T interaction.
Reason: PMID:27342281 reports reciprocal and endogenous human-cell coimmunoprecipitation, RNase resistance, and loss of UNR association after deleting 4E-T motif I. Its UNR construct is the 767-residue product; the study also uses a 1–744 truncation. These data support the physical association although they are not a purified binary-binding assay. A specific translation-regulatory role is plausible, but the authors retain alternatives for the combined motif-I/CHD repression phenotype. EIF4ENIF1/4E-T is a translational regulator, not automatically a canonical translation-initiation factor for purposes of a binding-class refinement. The generic positive is retained as non-core.
Supporting Evidence:
PMID:27342281
the novel 4E-T-UNR RNA-independent interaction was confirmed with endogenous proteins
GO:0005737 cytoplasm
IEA
GO_REF:0000044
MODIFY
Summary: Refine the supported cytoplasmic location to cytosol.
Reason: The localization mapping is broadly correct. HeLa cytosolic complexes and the dominant cytosolic pool in the 2025 fractionation support the more precise cytosol; context-dependent membrane-associated and other pools are not excluded.
Propagation Review
Root cause: NO FAILURE CORE
Sources checked:
UniProtKB-SubCell:SL-0086 SUPPORTS TRANSFER
The broad cytoplasm mapping is true; cytosol refines the experimentally observed pool without excluding other locations.
Proposed replacements: cytosol
GO:0005829 cytosol
IDA
GO_REF:0000052
ACCEPT
Summary: The cytosolic localization is supported by target-specific immunofluorescence curation.
Reason: The current Human Protein Atlas record is explicitly CSDE1/ENSG00000009307/O75534, with supported immunofluorescence reliability and cytosol as the main location. Antibodies HPA018846 and HPA052221 and additional ER/Golgi/plasma-membrane signals are retained in the evidence index. Cytosol is consistent with the molecular RNA-regulatory studies, without asserting exclusive localization.
Propagation Review
Root cause: NO FAILURE CORE
Sources checked:
UniProtKB:O75534 SUPPORTS TRANSFER
Actual HPA target record reports supported cytosol as the main IF location; other locations are not erased.
GO:0005829 cytosol
IDA
PMID:11051545
A mechanism for translationally coupled mRNA turnover: inter...
ACCEPT
Summary: Retain cytosolic localization of the human mCRD-associated pool.
Reason: The recovered 2000 original directly isolates endogenous complexes from human HeLa cytoplasmic lysate. Its source-specific localization is retained.
GO:0006446 regulation of translational initiation
ISS
GO_REF:0000024
ACCEPT
Summary: Retain regulation of translational initiation at the broad, direction-neutral level.
Reason: The supplied ortholog B7Z0E2 is Drosophila Unr. Its current GOA has experimental negative-regulation-of-initiation annotations rather than the exact broad term; GO:0045947 is an explicit child of the current GO:0006446 definition. This is compatible descendant support, not a missing donor function. Independent mammalian RNA/IRES studies support regulation at initiation. The fly-specific msl-2 context is not projected onto human CSDE1, and no single regulatory sign is imposed on all targets.
Propagation Review
Root cause: NO FAILURE CORE
Sources checked:
UniProtKB:B7Z0E2 SUPPORTS TRANSFER
Current experimental GO:0045947 assertions support the broader initiation-regulation concept; exact historical broad-row absence is distinguished from loss.
GO:0008584 male gonad development
TAS
PMID:2204029
Characterization of unr; a gene closely linked to N-ras.
MARK AS OVER ANNOTATED
Summary: Developmental testis expression does not establish execution of male gonad development.
Reason: All nine original pages of PMID:2204029 were inspected, including the mouse 13-day versus 49-day testis Northern comparison and Figure 8. The positive observation is increased Unr transcript abundance during testicular maturation. The study does not perturb Unr to establish gonadal morphogenesis or an executed developmental step. GO:0008584 describes progression of the male gonad to maturity, so this expression observation is insufficient for that specific participation claim. This does not deny expression in testis or exclude a developmental function supported by other evidence.
Supporting Evidence:
PMID:2204029
an increase in expression occurring upon testicular maturation
GO:0010494 cytoplasmic stress granule
IEA
GO_REF:0000044
KEEP AS NON CORE
Summary: Retain stress-granule localization as a regulated cellular context.
Reason: SL-0496 maps exactly to cytoplasmic stress granule, and the official target record traces the assertion to PMID:29395067. The available complete abstract explicitly identifies CSDE1 among core stress-granule proteins and reports a formation phenotype. Full target-level localization Methods and supplementary data were not recovered, so no additional construct or condition is invented. The existing positive localization is retained with curator deference as context-specific rather than a constitutive core location.
Propagation Review
Root cause: NO FAILURE NON CORE
Sources checked:
UniProtKB-SubCell:SL-0496 SUPPORTS TRANSFER
Exact stress-granule vocabulary mapping and target-source annotation are corroborated by the source abstract; detailed assay access remains limited.
GO:0034063 cytoplasmic stress granule assembly
IMP
PMID:29395067
High-Density Proximity Mapping Reveals the Subcellular Organ...
KEEP AS NON CORE
Summary: Retain the measured stress-granule assembly phenotype.
Reason: The complete PMID:29395067 abstract explicitly reports CSDE1 as critical for microscopically visible stress-granule formation. This supports the existing IMP assertion at its experimental context, without inferring an autonomous condensation mechanism or a physiological role in every cell state. Full Methods/Results were not recovered through bounded alternative routes, and no unobserved assay details are claimed.
Supporting Evidence:
PMID:29395067
CSDE1, and PRRC2C) are critical for the formation of microscopically visible
GO:0035613 RNA stem-loop binding
IDA
PMID:17947529
Internal initiation of translation from the human rhinovirus...
ACCEPT
Summary: Retain experimentally mapped RNA stem-loop binding.
Reason: Original HRV-2 mapping supports binding structured RNA domains, including single-stranded bulges/loops. This is genuine RNA stem-loop binding, not proof of duplex-specific binding or a universal RNA-chaperone mechanism.
Supporting Evidence:
PMID:17947529
the binding sites of Unr to two distinct secondary structure domains
GO:0045727 positive regulation of translation
IMP
PMID:36354136
N(6) -methyladenosine-modified lncRNA ARHGAP5-AS1 stabilises...
MODIFY
Summary: Refine positive translation regulation to the cytoplasmic context.
Reason: The HepG2 and SK-HEP-1 experiments measure CSDE1-dependent VIM/RAC1 protein abundance, not translation rate or elongation directly. Their elongation interpretation cites earlier work. Independent recombinant human-derived UNR reconstitution in PMID:10049359 directly increases IRES-dependent translation in a cytoplasmic translation system, supporting GO:2000767 without relying on protein abundance alone. Retain this source-preserving refinement on the combined evidence; do not infer an elongation-specific activity or relabel the HCC assay as a rate measurement.
GO:0070934 CRD-mediated mRNA stabilization
IBA
GO_REF:0000033
ACCEPT
Summary: Retain inherited coding-region-dependent mRNA stabilization.
Reason: Coding-region determinant-dependent stabilization is experimentally supported for the c-FOS mCRD. The current biological-process definition is general and does not impose the narrower c-MYC-complex identity. The actual PTN000985585 IBD lies on the human lineage; the target experimental source is legitimate descendant evidence.
Propagation Review
Root cause: NO FAILURE CORE
Sources checked:
PANTHER:PTN000985585 SUPPORTS TRANSFER
The literal IBD is at this actual ancestor on the human path; descendant experimental evidence grounds the inherited activity.
GO:0070934 CRD-mediated mRNA stabilization
IDA
PMID:11051545
A mechanism for translationally coupled mRNA turnover: inter...
ACCEPT
Summary: Retain the measured mCRD reporter stabilization.
Reason: Ectopic UNR stabilizes the mCRD-bearing reporter by slowing poly(A) shortening. This measured state coexists with its required role in subsequent turnover; avoid a universal stabilizer-only description.
Supporting Evidence:
PMID:11051545
stabilized mCRD-containing mRNA by impeding deadenylation
GO:0070937 CRD-mediated mRNA stability complex
IBA
GO_REF:0000033
REMOVE
Summary: Remove the c-MYC-complex interpretation of the c-FOS mCRD evidence; retain the existing specific mCRD IBA.
Reason: Current GO:0106002 explicitly distinguishes the c-FOS mCRD/poly(A)-bridging assembly from the c-MYC CRD complex GO:0070937. The underlying UNR/PABP experiments establish the c-FOS assembly. Remove this mismatched complex assertion; the GO:0106002 IBA with the same GO_REF:0000033, PTN000985585 and O75534 donor is already present and retained. The removal addresses complex identity, not duplication alone: annotations with distinct evidence remain valuable. Preserve the original source tuple and the valid ancestral placement and experimental self-donation; no circularity or lineage failure is implied.
Propagation Review
Root cause: TERM SCOPING PROBLEM
Sources checked:
PANTHER:PTN000985585 UNRESOLVED
The PTN is an actual ancestor and target self-evidence is valid. The term-specific c-MYC-complex assertion mis-scopes c-FOS mCRD evidence; the separately inherited GO:0106002 is retained. This judgment does not challenge the node placement or the node's other functions.
GO:0070937 CRD-mediated mRNA stability complex
IDA
PMID:15314026
UNR, a new partner of poly(A)-binding protein, plays a key r...
MODIFY
Summary: Refine the experimentally studied complex to the c-FOS mCRD assembly.
Reason: The 2004 experiments examine the c-FOS mCRD complex and direct UNR-PABP contact. Current GO0106002 identifies that assembly; retain the original GO0070937 assertion as provenance.
GO:0070966 nuclear-transcribed mRNA catabolic process, no-go decay
IMP
PMID:15314026
UNR, a new partner of poly(A)-binding protein, plays a key r...
MODIFY
Summary: Replace no-go decay with the demonstrated deadenylation-dependent process.
Reason: UNR perturbation and PABP competition affect CCR4-dependent deadenylation and decay of an mCRD reporter. Initiation blockade or premature termination upstream of mCRD stabilizes the reporter, unlike the stalled-elongation surveillance specified by no-go decay. CCR4, not CSDE1, supplies the nuclease activity. CSDE1 itself binds the coding-region RNA and directly contacts PABP to organize the functional RNA-protein assembly, so participation is supported by molecular work as well as perturbation. GO:0000288 describes the multistep pathway, not just nuclease catalysis; the absence of intrinsic nuclease activity is therefore not a reason to replace it with a regulation-only term.
Supporting Evidence:
PMID:15314026
deadenylation step is coupled to ongoing translation
GO:0075522 IRES-dependent viral translational initiation
IDA
PMID:17947529
Internal initiation of translation from the human rhinovirus...
KEEP AS NON CORE
Summary: Retain viral IRES initiation as a contextual host-protein activity.
Reason: Retain directly demonstrated viral IRES initiation as a host-protein function in a viral RNA context, outside the compact endogenous regulatory core. No claim that all viral IRESs respond similarly.
GO:0106002 mCRD-mediated mRNA stability complex
IBA
GO_REF:0000033
ACCEPT
Summary: Retain membership in the mCRD-mediated mRNA stability complex.
Reason: The mCRD assembly identity agrees with its current definition and target-specific biochemical evidence. The literal IBD at PTN000985585 is on the human path; target self-donation supplies experimental grounding and is not circular evidence.
Propagation Review
Root cause: NO FAILURE CORE
Sources checked:
PANTHER:PTN000985585 SUPPORTS TRANSFER
The literal IBD is at this actual ancestor on the human path; descendant experimental evidence grounds the inherited activity.
GO:0106002 mCRD-mediated mRNA stability complex
IPI
PMID:11051545
A mechanism for translationally coupled mRNA turnover: inter...
ACCEPT
Summary: Retain human mCRD complex association at the measured scope.
Reason: Human HeLa affinity isolation, fractionation and nuclease-controlled co-IP support the mCRD complex; these do not fix every binary contact or unique stoichiometry.
GO:0106222 lncRNA binding
IPI
PMID:36354136
N(6) -methyladenosine-modified lncRNA ARHGAP5-AS1 stabilises...
KEEP AS NON CORE
Summary: Retain direct lncRNA association in the hepatocellular-carcinoma context.
Reason: Human lncRNA pulldown, endogenous RIP and deletion mapping support ARHGAP5-AS1 binding in HCC cells. Retain this contextual ligand interaction, without assigning CSDE1 the lncRNA-mediated ubiquitination-protection mechanism as an autonomous activity.
Supporting Evidence:
PMID:36354136
CSDE1 working as the interacting protein of the lncRNA
GO:0140517 protein-RNA adaptor activity
IBA
GO_REF:0000033
ACCEPT
Summary: Retain the inherited protein-RNA adaptor activity.
Reason: Protein-RNA coordination is supported by direct UNR-PABP/RNA experiments and purified fly UNR-MLE-roX2 reconstitution. The actual PTN000985585 IBD lies on the human path and the target sequence is present in the family alignment. The conserved adaptor activity is supported; Drosophila dosage compensation is not assigned to human CSDE1.
Propagation Review
Root cause: NO FAILURE CORE
Sources checked:
PANTHER:PTN000985585 SUPPORTS TRANSFER
The literal IBD is at this actual ancestor on the human path; descendant experimental evidence grounds the inherited activity.
GO:1900152 negative regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay
IDA
PMID:11051545
A mechanism for translationally coupled mRNA turnover: inter...
ACCEPT
Summary: Retain the observed inhibition of deadenylation in the overexpression state.
Reason: The original overexpression phenotype impedes deadenylation. This is one experimentally observed state of a bidirectional turnover regulator, not proof of intrinsic nuclease inhibition in every context.
GO:1905172 RISC complex binding
IDA
PMID:32161113
CSDE1 controls gene expression through the miRNA-mediated de...
ACCEPT
Summary: Retain CSDE1 association with the miRNA-induced silencing complex.
Reason: PMID:32161113 identifies CSDE1 in miRNA-associated complexes and reports RNase-resistant AGO2 association with deletion controls. Human HEK293T experiments are distinguished from mouse NIH3T3/P19 and fly assays. This is binding to an assembled regulatory complex, not proof of purified pairwise AGO2 contact. The study finds no role in core miRISC formation and no effect on CCR4–NOT recruitment, so neither assembly nor nuclease activity is inferred. RISC association fits the established post-transcriptional RNA-regulatory role.
Supporting Evidence:
PMID:32161113
interacts with AGO2 within miRNA-induced silencing complex
GO:1905172 RISC complex binding
IEA
GO_REF:0000120
ACCEPT
Summary: The automated RISC-binding inference has matching rule and experimental source support.
Reason: Current ARBA00086820 has two condition sets; only the Eukaryota plus FunFam 2.40.50.140:FF:000055 branch matches the actual human sequence annotations and lineage. The plant-specific alternative branch does not match. The mouse donor Q91W50 carries the exact IDA RISC-binding term from PMID:32161113; mouse coIP and human experiments in that paper support conservation at complex-association scope. ENSMUSP00000029446 is retained as the original supplied entity and linked through the official mouse product record, not silently replaced.
Propagation Review
Root cause: NO FAILURE CORE
Sources checked:
ARBA:ARBA00086820 SUPPORTS TRANSFER
The complete current rule was evaluated; branch 0 matches both FunFam and Eukaryota.
UniProtKB:Q91W50 SUPPORTS TRANSFER
The exact current mouse IDA GO:1905172 row cites PMID:32161113; species-specific assay limits are retained.
Ensembl:ENSMUSP00000029446 SUPPORTS TRANSFER
The supplied mouse Ensembl product is present on the official Q91W50 record.
GO:2000767 positive regulation of cytoplasmic translation
IDA
PMID:11051545
A mechanism for translationally coupled mRNA turnover: inter...
ACCEPT
Summary: Retain positive cytoplasmic translation with independent direct support.
Reason: Positive cytoplasmic-translation regulation is supported by independent recombinant UNR/IRES reconstitution in PMID:10049359. In PMID:11051545, the measured phenotype is reporter stabilization and reduced deadenylation; enhanced initiation is discussed as a model and prior result, not as a newly measured translation-rate experiment. The original IDA/source tuple is preserved while this distinction and independent support remain explicit.

Core Functions

Directly recognizes mRNA sequences, including c-FOS coding-region elements and exposed loops or bulges in structured viral IRES RNA. This RNA-contact function is distinct from coordinating protein partners and does not imply duplex-RNA specificity.

Molecular Function:
mRNA binding
Cellular Locations:
Supporting Evidence:

Binds RNA and coordinates regulatory proteins with RNA to control cytoplasmic translation and transcript stability. In the c-FOS mCRD assembly, direct PABP association links coding-region recognition to poly(A)-tail regulation; effects on stabilization versus turnover depend on translation and ribonucleoprotein state. CSDE1 also associates with AGO2-containing miRNA silencing complexes and decapping factors. These are additional contexts for post-transcriptional regulation; they do not establish a role in core miRISC assembly or CCR4-NOT recruitment.

Supporting Evidence:
  • PMID:15314026
    only PABP displays direct interaction with UNR in a RNA-independent manner.
  • PMID:10049359
    Recombinant unr acts synergistically with recombinant PTB to stimulate translation dependent on the rhinovirus IRES.
  • PMID:11051545
    stabilized mCRD-containing mRNA by impeding deadenylation
  • PMID:32161113
    interacts with AGO2 within miRNA-induced silencing complex

References

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Suggested Questions for Experts

Q: Which target-specific experiment supports the P-body location attributed to CSDE1 in PMID:32354837, distinct from localization of its 4E-T partner?

Q: How do RNA occupancy, PABP association and ribosome transit determine whether CSDE1 stabilizes an mCRD transcript or permits CCR4-dependent deadenylation?

Q: Which functional differences can be assigned to each of the five official protein sequences, rather than to study-specific isoform labels or tags?

Suggested Experiments

Experiment: Compare sequence-verified endogenous CSDE1 variants at matched abundance using transcript-specific translation and poly(A)-tail measurements, while independently measuring transcript stability.

Experiment: Test endogenous CSDE1 localization with validated reagents and P-body markers across defined basal and stress conditions, separating target localization from recruitment of 4E-T.

πŸ“š Additional Documentation

Notes

(CSDE1-notes.md)

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