Affinage

LSM7

U6 snRNA-associated Sm-like protein LSm7 · UniProt Q9UK45

Length
103 aa
Mass
11.6 kDa
Annotated
2026-06-10
34 papers in source corpus 17 papers cited in narrative 17 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

LSM7 is a conserved Sm-like protein that serves as a structural subunit of two distinct heptameric LSm rings governing mRNA turnover and snRNA metabolism (PMID:10761922, PMID:11333229). In the cytoplasm, LSM7 is part of the Lsm1-7 complex that co-immunoprecipitates with the decapping enzyme Dcp1 and its activator Pat1 and with mRNA, where it promotes mRNA decapping and protects mRNA 3'-ends from exosome-mediated trimming, functioning epistatically to 3'-to-5' degradation (PMID:10761922, PMID:11514438). RNA recognition by this complex depends on cooperative contributions from the Lsm ring, the C-terminal domain of Lsm1, and Pat1, which directly contacts RNA and confers preference for oligo(A) tails (PMID:22450758, PMID:25035297). Through this activity, the Pat1-Lsm complex selectively stabilizes a subset of autophagy-related (ATG) mRNAs under nitrogen starvation to support robust autophagy induction (PMID:30527663). In the nucleus, LSM7 is part of the Lsm2-8 complex that binds and stabilizes U6 snRNA, and it associates with box H/ACA snoRNAs and scaRNAs to modulate 2'-O-methylation and pseudouridylation of spliceosomal snRNAs, with its loss destabilizing snRNPs and producing aberrant splicing (PMID:11333229, PMID:15075370, PMID:42168358). Structurally, LSM7 adopts the canonical Sm fold and assembles with LSM5 and LSM6 into a hexameric LSm657 intermediate that incorporates further subunits en route to both heptameric rings (PMID:22001694, PMID:22615807). Under metabolic stress, yeast Lsm7 undergoes liquid-liquid phase separation driven by its intrinsically disordered region to seed stress granule formation, regulated upstream by a Sch9/Ypk1-sphingolipid-ubiquitin axis (PMID:35764627, PMID:39897563). In human breast cancer cells, LSM7 promotes metastasis by mediating CD44 alternative splicing under transcriptional control of TCF3 (PMID:39182568), and biallelic LSM7 variants that disrupt LSM complex assembly cause a neurodevelopmental disorder with CNS and oligodendrocyte defects (PMID:35047835).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2000 High

    Established that Lsm7, as part of a seven-subunit Lsm1-7 complex, is a positive effector of cytoplasmic mRNA decapping, distinct from the nuclear U6-associated Lsm2-8 complex.

    Evidence Yeast genetic loss-of-function across all seven Lsm subunits plus reciprocal co-immunoprecipitation with Dcp1, Pat1 and mRNA

    PMID:10761922

    Open questions at the time
    • Did not resolve how the Lsm ring recognizes target mRNAs
    • Did not establish the structural basis of complex assembly
  2. 2001 High

    Defined a protective function for the Lsm1-7/Pat1 complex at mRNA 3'-ends, placing it upstream of and epistatic to exosomal 3'-to-5' degradation.

    Evidence Yeast mutant analysis with suppressor/epistasis testing against exosome and Ski mutations and Northern detection of trimmed mRNAs

    PMID:11514438

    Open questions at the time
    • Did not identify the RNA features recognized for protection
    • Did not separate decapping from 3'-end protection biochemically
  3. 2001 Medium

    Linked Lsm5/6/7 to nuclear U6 snRNA biogenesis, revealing functional redundancy with the La homolog Lhp1p in stabilizing nascent U6.

    Evidence Yeast deletion and suppressor/epistasis analysis of LSM5, LSM6, LSM7 with LHP1

    PMID:11333229

    Open questions at the time
    • Genetic epistasis from a single lab without biochemical reconstitution
    • Did not define direct U6 contacts by Lsm7
  4. 2002 Medium

    Identified the first human LSM7 physical interactor, TACC1, raising the possibility of roles beyond canonical RNA metabolism.

    Evidence Yeast two-hybrid screen with GST pull-down and co-immunoprecipitation

    PMID:12165861

    Open questions at the time
    • Functional consequence of the interaction not established for LSM7
    • All assays from a single lab
  5. 2003 Medium

    Extended cytoplasmic Lsm1-7/Pat1 function to translation, showing its loss impairs BMV RNA translation at the elongation step rather than ribosome recruitment.

    Evidence Yeast polysome gradient sedimentation with conditional PRT1 allele epistasis

    PMID:12773554

    Open questions at the time
    • Mechanism of elongation defect not resolved
    • Generality beyond viral RNA not tested
  6. 2004 Medium

    Showed an Lsm2-7 subcomplex recognizes box H/ACA snoRNA snR5 via its 3' end and localizes to nucleoli, broadening Lsm RNA targets beyond U6.

    Evidence In vitro RNA-binding reconstitution, glycerol gradient and sequential IP, subcellular fractionation

    PMID:15075370

    Open questions at the time
    • Lsm binding was not required for snR5 pseudouridylation function
    • Physiological role of the interaction unresolved
  7. 2012 High

    Provided the structural basis for ring assembly, establishing LSm5/6/7 as a hexameric Sm-fold intermediate that nucleates both LSm1-7 and LSm2-8 rings.

    Evidence X-ray crystallography (2.5 Å), NMR, AUC and pull-down across human and S. pombe subcomplexes

    PMID:22001694 PMID:22615807

    Open questions at the time
    • Did not capture the fully assembled heptameric rings
    • Subunit addition order to native rings not fully defined
  8. 2014 High

    Dissected the determinants of RNA binding by the cytoplasmic complex, showing both the Lsm1 C-terminal domain and Pat1 are required, with Pat1 conferring oligo(A) recognition.

    Evidence Purified-complex reconstitution and in vitro RNA binding with domain deletion plus in vivo decay rescue

    PMID:22450758 PMID:25035297

    Open questions at the time
    • Specific Lsm7 RNA contacts not defined
    • Structure of the RNA-bound holocomplex not determined
  9. 2018 High

    Connected the protective Lsm1-7-Pat1 activity to a physiological program, showing it stabilizes ATG mRNAs to enable autophagy under nitrogen starvation, regulated by Pat1 dephosphorylation.

    Evidence RNA immunoprecipitation, mRNA stability assays and genetic epistasis with exosome mutants

    PMID:30527663

    Open questions at the time
    • Basis of ATG mRNA selectivity not defined
    • Signal controlling Pat1 dephosphorylation not fully resolved
  10. 2021 Medium

    Established LSM7 as a human disease gene, with biallelic variants disrupting LSM ring assembly and causing CNS and oligodendrocyte defects.

    Evidence Affinity purification-mass spectrometry of complex assembly plus zebrafish knockdown with CNS phenotyping

    PMID:35047835

    Open questions at the time
    • Which complex (LSM1-7 vs LSM2-8) drives the phenotype not separated
    • Cellular mechanism of leukodystrophy not defined
  11. 2022 Medium

    Revealed a non-ring function: Lsm7 phase separates via its intrinsically disordered region to seed stress granule formation.

    Evidence Genome-wide imaging screen, live-cell imaging, deletion phenotype and phase separation assays in yeast under 2-DG stress

    PMID:35764627

    Open questions at the time
    • Relationship between ring-bound and condensate pools unclear
    • Conservation of this function in humans not tested
  12. 2024 Medium

    Defined an oncogenic role for human LSM7, mediating CD44 alternative splicing to promote breast cancer metastasis under TCF3 transcriptional control.

    Evidence RIP-seq, splicing sequencing, transwell/wound-healing and orthotopic xenograft assays, luciferase and ChIP

    PMID:39182568

    Open questions at the time
    • Whether CD44 splicing requires a specific LSM ring not established
    • Direct splicing mechanism versus indirect effect not resolved
  13. 2025 Medium

    Mapped the upstream signaling controlling Lsm7 phase separation, ordering a Sch9/Ypk1-sphingolipid-Ubp3-ubiquitin axis that gates condensate formation.

    Evidence High-content imaging phenomic screens with genetic epistasis of pathway components

    PMID:39897563

    Open questions at the time
    • Direct molecular trigger of Lsm7 demixing by ubiquitin not defined
    • Pathway from a single lab
  14. 2026 Medium

    Detailed the nuclear LSM2-8 role of LSM7 in Cajal bodies, governing U6 stability and directing scaRNA-mediated snRNA modification, with loss impairing spermatogonial stem cell differentiation.

    Evidence Genetic knockout, interaction assays with scaRNAs, snRNA modification and RNA-seq splicing analysis, differentiation assays

    PMID:42168358

    Open questions at the time
    • Direct versus indirect role in snRNA modification not fully separated
    • Tissue specificity of the differentiation phenotype not explained

Open questions

Synthesis pass · forward-looking unresolved questions
  • How LSM7's two ring contexts, its phase-separation behavior, and its disease/oncogenic activities are mechanistically integrated remains unresolved.
  • No structure of the RNA-bound heptameric rings containing LSM7
  • Unclear whether human LSM7 phase separation parallels yeast Lsm7
  • Causal link between specific ring defects and the human neurodevelopmental phenotype not dissected

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 6 GO:0005198 structural molecule activity 3
Localization
GO:0005634 nucleus 2 GO:0005829 cytosol 2 GO:0005730 nucleolus 1
Pathway
R-HSA-8953854 Metabolism of RNA 4 R-HSA-9612973 Autophagy 1
Partners
DCP1LSM5LSM6PATL1TACC1
Complex memberships
LSm5/6/7 (LSm657) subcomplexLsm1-7-Pat1 complexLsm2-8 complex

Evidence

Reading pass · 17 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 Lsm1-Lsm7 proteins (including Lsm7) form a complex that co-immunoprecipitates with the mRNA decapping enzyme Dcp1, the decapping activator Pat1/Mrt1, and with mRNA. Mutations in any of the seven Lsm proteins (Lsm1-Lsm7) inhibit mRNA decapping, establishing that this complex promotes mRNA decapping. The Lsm1-7 complex is distinct from the nuclear U6-associated Lsm2-8 complex. Genetic mutant analysis (yeast), co-immunoprecipitation Nature High 10761922
2001 The Lsm1-7/Pat1 complex protects mRNA 3'-UTRs from 3'-end trimming (shortening by 10-20 nt). Mutations in LSM1-LSM7 or PAT1 lead to accumulation of trimmed mRNAs. Temperature-sensitive growth of lsm mutants is suppressed by mutations in the exosome or Ski proteins, indicating the exosome degrades trimmed mRNAs and that Lsm/Pat1 function is epistatic to 3'-to-5' degradation. Genetic mutant analysis (yeast), epistasis with exosome/Ski mutations, Northern blot analysis of trimmed mRNA Genetics High 11514438
2001 Deletion of LSM5, LSM6, or LSM7 causes the La protein homolog Lhp1p to become required for growth, indicating functional redundancy between these Lsm subunits and Lhp1p in stabilizing nascent U6 snRNA. The Lsm2-8 complex (which includes Lsm7) binds and stabilizes U6 snRNA. Genetic deletion analysis in yeast, suppressor analysis, genetic epistasis Genetics Medium 11333229
2003 The Lsm1p-7p/Pat1p complex (including Lsm7) is required for translation of brome mosaic virus (BMV) genomic RNAs. Mutation of LSM7 combined with a conditional translation initiation factor (PRT1) allele showed that the Lsm1-7/Pat1 complex defect inhibits BMV RNA translation primarily by stalling or slowing ribosome elongation, not by preventing ribosome association. Yeast genetic analysis, sucrose density gradient sedimentation (polysome analysis), conditional allele epistasis Molecular and cellular biology Medium 12773554
2002 Human LSM7 protein physically interacts with TACC1 (transforming acidic coiled-coil 1), identified by yeast two-hybrid screen, GST pull-down, and co-immunoprecipitation. Yeast two-hybrid screen, GST pull-down, co-immunoprecipitation Oncogene Medium 12165861
2003 Human LSM7 physically interacts with TACC1, chTOG, TRAP, and Aurora A as part of a protein complex, confirmed by co-immunoprecipitation and interaction mapping. Co-immunoprecipitation, protein interaction delineation Oncogene Low 14603251
2004 An Lsm2-Lsm7 subcomplex (lacking Lsm1 and Lsm8) associates with the box H/ACA snoRNA snR5. In vitro reconstitution showed the 3' end of snR5 is critical for Lsm protein recognition. Lsm proteins are present in nucleoli. However, Lsm proteins are not required for snR5's function in pseudouridylation of rRNA. In vitro reconstitution of RNA binding, glycerol gradient sedimentation, sequential immunoprecipitation, subcellular fractionation/localization Molecular biology of the cell Medium 15075370
2011 Crystal structure of the LSm5/6/7 subcomplex (LSm657) at 2.5 Å resolution shows each subunit adopts the canonical Sm fold and arranges into a hexameric ring. NMR confirmed hexameric assembly in solution. Pull-down and NMR experiments showed LSm657 can incorporate LSm23 to assemble further toward native LSm rings, identifying LSm657 as an assembly intermediate for both LSm1-7 and LSm2-8 complexes. X-ray crystallography (2.5 Å), NMR spectroscopy, pull-down assay Journal of molecular biology High 22001694
2012 Crystal structures of the Lsm5/6/7 subcomplex from S. pombe reveal all three subunits share a conserved Sm fold; Lsm5/6/7 forms a hexamer in the crystal and in solution (by analytical ultracentrifugation). RNA binding assays showed that the Lsm5/6/7 subcomplex binds oligo(U), and the inter-subunit organization order among Lsm5, Lsm6, and Lsm7 was determined. X-ray crystallography, analytical ultracentrifugation, in vitro RNA binding assay PloS one High 22615807
2012 The Lsm1-7-Pat1 complex RNA-binding activity requires both the Sm-domain and the C-terminal domain (CTD) of Lsm1. Deletion of the Lsm1 CTD impairs mRNA decay in vivo and severely impairs RNA binding of the Lsm1-7-Pat1 complex (which contains Lsm7) in vitro. Overexpression of the CTD polypeptide in trans can suppress the decay and 3'-end protection defects. Purified complex RNA binding assay in vitro, in vivo mRNA decay assay, domain deletion and trans-complementation RNA (New York, N.Y.) Medium 22450758
2014 Pat1 contributes critically to the RNA binding activity of the Lsm1-7-Pat1 complex (which includes Lsm7). The Lsm1-7 complex purified from pat1Δ cells has very low RNA binding activity and cannot recognize the oligo(A) tail. Reconstitution of Lsm1-7-Pat1 from these components restores RNA binding and oligo(A) preference. Pat1 directly contacts RNA within the complex. The middle domain of Pat1 is essential for its interaction with the Lsm1-7 complex. Purified complex reconstitution, in vitro RNA binding assay, domain deletion analysis RNA (New York, N.Y.) High 25035297
2018 The Pat1-Lsm (Lsm1-Lsm7) complex binds a specific subset of autophagy-related (ATG) mRNAs under nitrogen starvation and prevents their 3'-to-5' degradation by the exosome, leading to ATG mRNA stabilization. This process is regulated through Pat1 dephosphorylation and is required for robust autophagy induction during nitrogen starvation. RNA immunoprecipitation, mRNA stability assays, genetic loss-of-function, epistasis with exosome mutants Molecular cell High 30527663
2021 Pathogenic biallelic variants in LSM7 disrupt assembly of both the LSM1-7 and LSM2-8 complexes, as shown by affinity purification-mass spectrometry. LSM7 knockdown in zebrafish causes central nervous system defects including impaired oligodendrocyte development and motor behavior deficits. Affinity purification-mass spectrometry, zebrafish knockdown with CNS phenotyping HGG advances Medium 35047835
2022 Under 2-deoxy-D-glucose-induced stress in yeast, Lsm7 rapidly forms foci via liquid-liquid phase separation driven by its intrinsically disordered region and hydrophobic clusters. These Lsm7 phase-separated condensates act as seeding scaffolds that promote Pab1 demixing and subsequent stress granule (SG) initiation. Deletion of Lsm7 significantly decreases SG formation. Genome-wide imaging-based phenomic screen, live-cell fluorescence imaging, deletion mutant analysis, phase separation assays Nature communications Medium 35764627
2024 Human LSM7 binds CD44 RNA (shown by RIP-seq) and enhances expression of the alternatively spliced CD44s isoform. LSM7 overexpression increases migration and invasion of breast cancer cells and promotes spontaneous lung metastasis in vivo. The transcription factor TCF3 activates LSM7 transcription by directly binding to the LSM7 promoter (luciferase reporter and ChIP assays). RNA immunoprecipitation-sequencing (RIP-seq), third-generation sequencing, transwell/wound healing assays, orthotopic xenograft, luciferase reporter assay, chromatin immunoprecipitation Life sciences Medium 39182568
2025 A signaling pathway regulates Lsm7 phase separation and stress granule formation: Sch9/Ypk1 kinases act upstream to decrease intermediate long-chain base sphingolipids, which downregulates the deubiquitinase Ubp3, leading to decreased free ubiquitin levels that facilitate Lsm7 phase separation and trigger stress granule formation. High-content imaging-based phenomic screens, genetic analysis of signaling pathway components Theranostics Medium 39897563
2026 LSM7, as a component of the LSM2-8 complex, governs U6 snRNA stability within Cajal bodies and directly interacts with scaRNA2, scaRNA13, and scaRNA17 to modulate 2'-O-methylation and pseudouridylation of U2 and U12 snRNAs. Loss of LSM7 causes defective nuclear localization and reduced stability of U2, U5, and U6 snRNAs, destabilizes corresponding snRNP complexes, and produces aberrant splicing events (affecting mutually exclusive exons and exon skipping), ultimately impairing spermatogonial stem cell differentiation. Genetic knockout, co-immunoprecipitation/interaction assays, snRNA modification analysis, RNA-seq splicing analysis, cell differentiation assays Cell death and differentiation Medium 42168358

Source papers

Stage 0 corpus · 34 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 Yeast Sm-like proteins function in mRNA decapping and decay. Nature 351 10761922
2013 A genome-wide RNAi screen reveals that mRNA decapping restricts bunyaviral replication by limiting the pools of Dcp2-accessible targets for cap-snatching. Genes & development 82 23824541
2001 The yeast cytoplasmic LsmI/Pat1p complex protects mRNA 3' termini from partial degradation. Genetics 82 11514438
2003 TACC1-chTOG-Aurora A protein complex in breast cancer. Oncogene 79 14603251
2003 Yeast Lsm1p-7p/Pat1p deadenylation-dependent mRNA-decapping factors are required for brome mosaic virus genomic RNA translation. Molecular and cellular biology 75 12773554
2001 Multiple functional interactions between components of the Lsm2-Lsm8 complex, U6 snRNA, and the yeast La protein. Genetics 65 11333229
2002 Carcinogenesis and translational controls: TACC1 is down-regulated in human cancers and associates with mRNA regulators. Oncogene 59 12165861
2014 Role for LSM genes in the regulation of circadian rhythms. Proceedings of the National Academy of Sciences of the United States of America 56 25288739
2009 To bleed or not to bleed. A prediction based on individual gene profiling combined with dose-volume histogram shapes in prostate cancer patients undergoing three-dimensional conformal radiation therapy. International journal of radiation oncology, biology, physics 42 19211196
2023 Proteomics and transcriptomics explore the effect of mixture of herbal extract on diabetic wound healing process. Phytomedicine : international journal of phytotherapy and phytopharmacology 41 37267693
2004 An Lsm2-Lsm7 complex in Saccharomyces cerevisiae associates with the small nucleolar RNA snR5. Molecular biology of the cell 37 15075370
2014 Pat1 contributes to the RNA binding activity of the Lsm1-7-Pat1 complex. RNA (New York, N.Y.) 35 25035297
2018 The Pat1-Lsm Complex Stabilizes ATG mRNA during Nitrogen Starvation-Induced Autophagy. Molecular cell 34 30527663
2015 Genome-Wide Identification and Validation of Reference Genes in Infected Tomato Leaves for Quantitative RT-PCR Analyses. PloS one 34 26313760
2022 Lsm7 phase-separated condensates trigger stress granule formation. Nature communications 16 35764627
2012 Both Sm-domain and C-terminal extension of Lsm1 are important for the RNA-binding activity of the Lsm1-7-Pat1 complex. RNA (New York, N.Y.) 15 22450758
2012 Crystal structures of Lsm3, Lsm4 and Lsm5/6/7 from Schizosaccharomyces pombe. PloS one 15 22615807
2012 A molecular computational model improves the preoperative diagnosis of thyroid nodules. BMC cancer 15 22958914
2011 Structure of the LSm657 complex: an assembly intermediate of the LSm1-7 and LSm2-8 rings. Journal of molecular biology 15 22001694
2024 Machine learning nominates the inositol pathway and novel genes in Parkinson's disease. Brain : a journal of neurology 14 37804111
2022 Comprehensive analysis of spliceosome genes and their mutants across 27 cancer types in 9070 patients: clinically relevant outcomes in the context of 3P medicine. The EPMA journal 11 35719132
2021 Variants in LSM7 impair LSM complexes assembly, neurodevelopment in zebrafish and may be associated with an ultra-rare neurological disease. HGG advances 10 35047835
2019 Towards understanding mRNA-binding protein specificity: lessons from post-transcriptional regulation of ATG mRNA during nitrogen starvation-induced autophagy. Current genetics 5 30783742
2024 RNA-binding protein LSM7 facilitates breast cancer metastasis through mediating alternative splicing of CD44. Life sciences 3 39182568
2025 Stress granule formation is regulated by signaling machinery involving Sch9/Ypk1, sphingolipids, and Ubi4. Theranostics 2 39897563
2024 LSM7 variants involving key amino acids for LSM complex function cause a neurodevelopmental disorder with leukodystrophy and cerebellar atrophy. HGG advances 2 39420558
2022 PLPP2: Potential therapeutic target of breast cancer in PLPP family. Immunobiology 2 36332491
2020 Species and tissue specific analysis based on quantitative proteomics from allotetraploid and the parents. Journal of proteomics 2 33309926
2026 Single-cell and multi-omics analysis identifies mitophagy-related biomarkers and therapeutic targets in ischemic stroke. Scientific reports 0 41792398
2026 Ion-Channel-Mediated Drug Repurposing Opportunities Validated by Single-Cell Perturbation in Colorectal Cancer. International journal of molecular sciences 0 42074061
2026 LSM7 coordinates scaRNA-mediated snRNA modification to ensure spliceosome fidelity and spermatogonial stem cell differentiation. Cell death and differentiation 0 42168358
2025 Analysis of mouse lens morphological and proteomic abnormalities following deletion of the βB3-crystallin promoter. Experimental eye research 0 40840647
2024 Analysis of mouse lens morphological and proteomic abnormalities following depletion of βB3-crystallin. bioRxiv : the preprint server for biology 0 39803551
2016 Mutagenic Analysis of the C-Terminal Extension of Lsm1. PloS one 0 27434131

Missed literature

Know a paper Affinage missed for LSM7? Flag it for the maintainers and the community.

No submissions yet.