Lsm6 is a small (75-residue) Sm-fold protein of fission yeast and one of the seven subunits shared by two heteroheptameric Lsm rings that bind the 3' ends of RNAs. In the nucleus it is part of the Lsm2-8 ring, which binds the 3' oligouridylate tail of U6 snRNA, preferring the 2',3'-cyclic phosphate end produced by Usb1, and acts as a chaperone for U6 in the U6 snRNP, the U4/U6.U5 tri-snRNP and spliceosome assembly. In fission yeast the same Lsm2-8 ring also binds the telomerase RNA TER1 and is a component of the telomerase holoenzyme, where it protects TER1 and promotes assembly with the reverse transcriptase Trt1 and the LARP7 protein Pof8. In the cytoplasm Lsm6 is part of the Lsm1-7 ring, which loads onto the 3' ends of oligouridylated or deadenylated mRNAs and, with Pat1, activates decapping and 5'-3' mRNA decay in P-bodies. Within both rings Lsm6 sits between Lsm3 and Lsm5, and an Lsm5-Lsm6-Lsm7 subcomplex is an assembly intermediate of both rings and binds oligo(U) RNA on its own.
Summary: Lsm6 takes part in pre-mRNA splicing as a subunit of the U6-binding Lsm2-8 ring.
Reason: The IBA comes from a deep PANTHER node (PTN000111530) that spans both the SmF and Lsm6 branches of PTHR11021, and splicing is shared by both branches (SmF via U1/U2/U4/U5 Sm rings, Lsm6 via the U6-associated Lsm2-8 ring), so placing the claim at this depth is sound. For S. pombe Lsm6 specifically, the Lsm2-8 ring binds the U6 snRNA 3' end and acts as a U6 chaperone, which is direct structural participation in splicing, not merely a requirement for it.
Summary: InterPro2GO from the Lsm6/SmF entry; consistent with the Lsm2-8 role in U6 function.
Reason: IPR016487 covers both SmF and Lsm6, both of which act in splicing through their respective rings, so this family-level mapping holds for Lsm6. Consistent with the IBA and NAS rows for the same term.
NAS PMID:32518066 Molecular basis for the distinct cellular functions of the L...
ACCEPT
Summary: Author statement that the S. pombe Lsm2-8 complex chaperones U6 spliceosomal RNA.
Reason: PMID:32518066 studies S. pombe Lsm2-8 directly, including crystal structures containing Lsm6 bound to U6-like RNA; its statement of the U6 chaperone role supports participation in splicing.
Summary: Lsm1-7, which includes Lsm6, acts in P-bodies; inherited from the Lsm6-specific PAINT node.
Reason: PTN000111600 is the Lsm6 subfamily node (PTHR11021:SF1), which contains S. pombe lsm6 and the budding-yeast LSM6 donor (SGD:S000002786). The Lsm1-7 ring forms and acts in P-bodies, and fission yeast Lsm6 is an experimentally established Lsm1-7 subunit. Location of a core activity.
Summary: RNA binding is correct but general; S. pombe evidence supports poly(U) RNA binding.
Reason: Correct family-wide inference (lsm6 itself is among the donors, consistent with its own experimental binding data). The S. pombe evidence supports the more specific poly(U) RNA binding, which the gene already carries by IDA, and the Lsm2-8 ring binds the U6 snRNA 3' end.
Propagation Review
Root cause:NO FAILURE CORE
Sources checked:
PANTHER:PTN000111529SUPPORTS TRANSFER
Deep SmF/Lsm6 family node covering lsm6; RNA binding is shared by every branch. The MODIFY only refines to the more specific term the target already carries experimentally.
IPI PMID:22615807 Crystal structures of Lsm3, Lsm4 and Lsm5/6/7 from Schizosac...
REMOVE
Summary: Interaction with Lsm5 within the Lsm5/6/7 subcomplex; generic protein binding is uninformative.
Reason: The Lsm6-Lsm5 contact is real (crystal structure of the Lsm5/6/7 subcomplex) but is the inter-subunit packing of the Lsm ring, already captured by Lsm2-8 complex and Lsm1-7-Pat1 complex membership. Bare protein binding adds no functional information; removal does not mean the interaction is false.
IPI PMID:22615807 Crystal structures of Lsm3, Lsm4 and Lsm5/6/7 from Schizosac...
REMOVE
Summary: Interaction with Lsm7 within the Lsm5/6/7 subcomplex; generic protein binding is uninformative.
Reason: As for the Lsm5 row, this is ring-subunit packing already captured by the complex memberships; bare protein binding is uninformative. Removal does not mean the interaction is false.
HDA PMID:16823372 ORFeome cloning and global analysis of protein localization ...
ACCEPT
Summary: Nuclear localization from the genome-wide YFP localization screen; matches the Lsm2-8 pool.
Reason: The ORFeome screen is abstract-only here, but a nuclear pool is fully consistent with the nuclear Lsm2-8 ring (U6 snRNP, telomerase). Accept and defer to the curator.
Next, we determined the localization of 4,431 proteins, corresponding to approximately 90% of the fission yeast proteome, by tagging each ORF with the yellow fluorescent protein.
IDA PMID:26292707 Structure of a yeast spliceosome at 3.6-angstrom resolution.
UNDECIDED
Summary: Possibly attached to the wrong gene product; Lsm6 is not in the deposited PMID:26292707 spliceosome model, whose U5 Sm ring contains SmF (smf1). Unverified against the full text, so left undecided and raised with PomBase as a source defect.
Reason: PMID:26292707 is the 3.6-angstrom cryo-EM structure of an S. pombe spliceosome (PDB 3JB9). Its U2 and U5 snRNPs carry canonical Sm rings (SmB/D1/D2/D3/E/F/G). A live UniProt query of all entries cross-referencing 3JB9 returns 27 S. pombe proteins including all seven Sm proteins and smf1 (SmF), but no Lsm protein at all, and Lsm6 lists only Lsm-ring structures. Lsm6 is also not an Sm-ring subunit on any evidence; its PANTHER subfamily (PTHR11021:SF1) is the Lsm6 branch, distinct from the SmF branch. In QuickGO, lsm6 is the only one of the queried Sm-family proteins carrying PMID:26292707 annotations, while smf1 carries none. This is not an inference from a title; the deposited model of the cited paper does not contain this protein. The most likely explanation is a SmF/Lsm6 mix-up within the SmF/LSm6 family. However, the PDB cross-reference shows only what was modelled, not what was in the purified particle or in the paper's compositional data, and the cached publication is abstract-only. The curator may have used evidence not visible here, so this experimental row is UNDECIDED rather than removed; the proposed correction (to smf1) is carried by the source defect for PomBase to check.
EXP PMID:26292707 Structure of a yeast spliceosome at 3.6-angstrom resolution.
UNDECIDED
Summary: Possibly attached to the wrong gene product; Lsm6 is not in the deposited PMID:26292707 spliceosome model, whose U2 Sm ring contains SmF (smf1). Unverified against the full text, so left undecided.
Reason: Same evidence and same caveat as the U5 snRNP row from this paper. The 3JB9 model contains SmF and the other canonical Sm proteins but no Lsm subunit, but a deposited model does not establish full particle composition and the full text has not been seen. UNDECIDED pending PomBase's check of the source defect.
EXP PMID:35277511 The methyl phosphate capping enzyme Bmc1/Bin3 is a stable co...
ACCEPT
Summary: Lsm2-8 co-purifies with the catalytically active S. pombe telomerase holoenzyme.
Reason: Mass spectrometry of Bmc1 immunoprecipitates identified the Lsm2-8 complex together with Pof8 and Trt1 as the core telomerase holoenzyme. Fission-yeast-specific role of Lsm2-8 in TER1 binding; Lsm6 is a shared Lsm2-8 subunit.
Summary: Nucleolar Lsm activity inherited from budding-yeast LSM6 at the Lsm6 subfamily node.
Reason: The PAINT node is the Lsm6 branch, which contains the target, and there is no S. pombe evidence of loss. The nucleolar role (Lsm2-7 with snoRNA/pre-rRNA in budding yeast) is not tested in fission yeast and is peripheral to the Lsm2-8 and Lsm1-7 roles.
Summary: snoRNP membership inherited from budding-yeast LSM6 (Lsm2-7 with snoRNA).
Reason: PAINT placed this at the Lsm6 subfamily node containing the target; no fission yeast data either way. Retain as a peripheral, phylogenetically inherited role.
Summary: Cytoplasmic pool corresponds to the Lsm1-7 ring.
Reason: Lsm6 is an experimentally established subunit of the cytoplasmic Lsm1-7 complex in S. pombe; the diffuse cytoplasmic pool as well as P-bodies is expected.
IDA PMID:22615807 Crystal structures of Lsm3, Lsm4 and Lsm5/6/7 from Schizosac...
ACCEPT
Summary: Recombinant S. pombe Lsm5/6/7 subcomplex binds oligo(U).
Reason: Direct S. pombe assay on a subcomplex containing Lsm6. The physiological binder is the heptameric ring, so this is a contribution to the ring's oligo(U) binding; the Lsm2-8 and Lsm1-7 RNA-bound structures (PMID:32518066) confirm oligoU recognition by the full rings.
IDA PMID:26292707 Structure of a yeast spliceosome at 3.6-angstrom resolution.
UNDECIDED
Summary: Possibly attached to the wrong gene product; the U2 Sm ring in the cited structure contains SmF, not Lsm6. Unverified against the full text, so left undecided.
Reason: Same evidence and same caveat as the U2/U5 snRNP rows from PMID:26292707. Lsm6 is absent from the deposited 3JB9 model, and U2 snRNA binding by an Sm ring belongs to the canonical Sm proteins, but the full text has not been seen. UNDECIDED pending PomBase's check of the source defect.
The molecular basis for the Lsm2–8 interaction with U6 snRNA terminating in a cyclic phosphate has yet to be elucidated, despite existing cryo-EM structures of the human U4/U6.U5 tri-snRNP (Agafonov et al. 2016) and pre-B complex (Charenton et al. 2019), both of which contain the Lsm2–8 complex bound to U6 snRNA.
EXP PMID:22001694 Structure of the LSm657 complex: an assembly intermediate of...
ACCEPT
Summary: S. pombe LSm657 assembly intermediate incorporates LSm2/3 toward the native Lsm2-8 ring.
Reason: Abstract-only here, but the paper's structure, NMR and pull-downs on S. pombe Lsm5/6/7 and Lsm2/3 support Lsm2-8 membership, confirmed independently by PMID:32518066.
NAS PMID:32518066 Molecular basis for the distinct cellular functions of the L...
ACCEPT
Summary: Lsm2-8 promotes telomerase biogenesis in S. pombe by binding TER1.
Reason: Lsm2-8 is itself a structural RNA-binding component of the telomerase RNP, binding the TER1 3' end and promoting Trt1 association, so it does part of the assembly work rather than merely being required for it. Fission-yeast-specific, non-catalytic.
TAS PMID:29422501 LARP7 family proteins have conserved function in telomerase ...
ACCEPT
Summary: Lsm2-8 binds TER1 alongside Lar7/Pof8 and Trt1 to form the telomerase RNP.
Reason: PMID:29422501 assays Lsm3 as the tagged Lsm2-8 subunit; transfer to Lsm6 is at the level of the ring, of which Lsm6 is an established subunit. Consistent with the NAS row.
IDA PMID:32518066 Molecular basis for the distinct cellular functions of the L...
NEW
Summary: Lsm6 contributes to the U6 3'-end binding activity of the S. pombe Lsm2-8 ring.
Reason: S. pombe Lsm2-8 crystal structures (PDB 6PPN/6PPP, Lsm6 chains F/N) and fluorescence polarization show specific binding of the U6 3' oligoU end terminating in a 2',3' cyclic phosphate. The ring, not the monomer, is the binder, so contributes_to. This is more specific than the existing RNA binding/poly(U) RNA binding and is the activity behind the U6 snRNP role.
pombe Lsm2–8 preferentially binds RNA that has been processed by Usb1.
Core Functions
Subunit of the nuclear Lsm2-8 ring that binds the 3' oligoU end of U6 snRNA (preferring the 2',3'-cyclic phosphate) and chaperones U6 in the U6 snRNP and tri-snRNP during spliceosome assembly.
Q: Were the PomBase PMID:26292707 annotations (U2 snRNA binding, U2 snRNP, U5 snRNP) intended for smf1 (SmF) rather than lsm6, given that the 3JB9 model contains SmF and no Lsm subunit?
Q: The Lsm6 PAINT node (PTN000111600) propagates P-body but not decapping or mRNA decay terms; is decapping deliberately restricted to Lsm1, or should Lsm1-7 subunits carry a contributes_to decapping-related annotation?
Suggested Experiments
Experiment: Test whether lsm6 point mutants at the Lsm5/Lsm3 interfaces separately disrupt Lsm2-8 (U6 and TER1 levels) versus Lsm1-7 (mRNA decay) function in S. pombe.
External Prediction Reviews
These computational predictions are reviewed separately from the GOA annotation set used for this review. The assessments below are from this project and do not constitute official GO annotations or endorsement by GO/UniProt. They are not included in the existing annotation review above.
Lsm6 is a subunit of the experimentally established S. pombe Lsm1-7 and Lsm2-8 RNA-binding rings. The single ProtNLM2 prediction, Sm-like protein family complex, is correct but repeats a term the gene already carries in GOA.
Review rationale: Fission yeast crystallography and biochemical reconstitution place Lsm6 in the Lsm5/6/7 subcomplex and in the Lsm1-7 ring bound to RNA, so membership of an Sm-like protein family complex is correct. The identical term GO:0120114 is already annotated to Q9UUI1 in GOA (IEA, ARBA), and the gene also carries the more specific Lsm2-8 and Lsm1-7-Pat1 complex terms, so the prediction is not novel.
Supporting Evidence:
PMID:22615807: "RNA binding assays show that Lsm2/3 and Lsm5/6/7 bind to oligo(U) whereas no RNA binding is observed for Lsm3 and Lsm4. Analysis of the inter-subunit interactions in Lsm5/6/7 reveals the organization order among Lsm5, Lsm6 and Lsm7."
PMID:32518066: "The structure of S. pombe Lsm1–7 bound to RNA."