Affinage

LSM10

U7 snRNA-associated Sm-like protein LSm10 · UniProt Q969L4

Length
123 aa
Mass
14.1 kDa
Annotated
2026-06-10
19 papers in source corpus 14 papers cited in narrative 15 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

LSM10 (Lsm10) is a U7 snRNP-specific Sm-like protein that defines the noncanonical Sm core required for 3'-end processing of replication-dependent histone pre-mRNAs (PMID:11574479, PMID:19620235). It substitutes for Sm D1 in the heptameric Sm ring assembled around the special Sm-binding site of U7 snRNA, which dictates its selective incorporation (PMID:11574479), and this unique composition is conserved from Drosophila to mammals (PMID:14624008). Lsm10 functions as an obligate partner of Lsm11: the two form a heterodimer that serves as the precursor for U7 snRNP assembly by a specialized SMN complex lacking Sm D1/D2 (PMID:12975319, PMID:19620235), and is handed off through the PRMT5/MEP50/pICln methylosome, where PRMT5 binds Lsm11 but leaves Lsm10 unmethylated (PMID:16087681, PMID:37562960). Within the assembled U7 snRNP, Lsm10 together with SmB and SmD3 contacts histone pre-mRNA between the U7-binding site and the cleavage site, acting as a molecular ruler that defines the endonucleolytic cut (PMID:19470752), with recruitment to substrate occurring in a FLASH- and SLBP-dependent manner (PMID:28289156). Lsm10-containing U7 snRNP localizes to Cajal bodies and to histone locus bodies at the histone gene cluster (PMID:11574479, PMID:19277982), and beyond co-transcriptional processing it mediates transcriptional repression of histone genes outside S phase via hnRNP UL1 (PMID:22451911). Restoring Lsm10/Lsm11 levels enhances U7 snRNP assembly and rescues histone-processing and neuromuscular pathology in SMA mice, linking U7 snRNP function to spinal muscular atrophy disease biology (PMID:36130491).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 2001 High

    Established that U7 snRNP has a distinct protein composition by identifying Lsm10 as a novel Sm-like protein that replaces Sm D1, answering what makes U7 snRNP biochemically unique.

    Evidence Biochemical purification of U7 snRNPs from HeLa cells with microsequencing, plus immunofluorescence localization

    PMID:11574479

    Open questions at the time
    • Did not resolve how Lsm10 selectively recognizes the U7 Sm site at atomic resolution
    • Functional consequence of D1 replacement for processing not yet tested
  2. 2003 High

    Showed that the U7-specific Sm core is built by a specialized SMN complex acting on the noncanonical U7 Sm site, and that the unique composition is evolutionarily conserved.

    Evidence In vitro assembly assays and Co-IP with a specialized SMN complex; reciprocal Co-IP and cross-species assembly in Drosophila and mammalian cells

    PMID:12975319 PMID:14624008

    Open questions at the time
    • Order of Sm/Lsm loading onto the ring not defined
    • How the SMN complex discriminates the U7 Sm site mechanistically unresolved
  3. 2005 Medium

    Defined how Lsm10/Lsm11 enter the assembly chaperone pathway, showing they bind pICln and SMN without themselves being symmetrically dimethylated.

    Evidence In vivo and in vitro Co-IP, methylation assays, and SMN binding studies

    PMID:16087681

    Open questions at the time
    • Structural basis of the methylation-independent SMN interaction not determined
    • Single-lab finding
  4. 2006 Medium

    Demonstrated that U7 snRNP levels are limiting for assembly but that Lsm10 is essential for cell cycle progression, linking U7 snRNP function to proliferation.

    Evidence Histone 3'-end GFP reporter assay, RNAi knockdown, and flow cytometry cell cycle analysis in HeLa cells

    PMID:16914750

    Open questions at the time
    • Did not establish whether G1 arrest is a direct consequence of histone processing failure
    • Overexpression had no processing effect, leaving the rate-limiting step unclear
  5. 2009 High

    Revealed the catalytic logic and in vivo requirement of Lsm10, showing the Sm core acts as a molecular ruler for cleavage-site selection and that Lsm10 loss causes aberrant polyadenylated histone mRNA and mislocalization.

    Evidence Biotin pulldown and UV cross-linking of processing complexes; Drosophila Lsm10/Lsm11 null mutants with RT-PCR, immunostaining, and TMG IP; immunofluorescence/FISH in human cells

    PMID:19277982 PMID:19470752 PMID:19620235

    Open questions at the time
    • Identity of the endonuclease positioned by the ruler not addressed here
    • Cause of HLB-to-Cajal-body redistribution in cancer cells unexplained
  6. 2011 High

    Mapped the functional handoff from U7 snRNP to the processing machinery by showing FLASH–Lsm11 contact is essential for processing independently of HLB localization.

    Evidence Drosophila genetic rescue with site-directed mutagenesis and in vitro binding/dominant-negative analysis

    PMID:21525146

    Open questions at the time
    • Direct role of Lsm10 (vs Lsm11) in the FLASH contact not separated
    • How FLASH bridges to the catalytic step not resolved
  7. 2012 Medium

    Uncovered a second, transcriptional role for Lsm10-containing U7 snRNP in repressing histone genes outside S phase via hnRNP UL1.

    Evidence siRNA knockdown, pulse-chase, mass spectrometry of captured U7 snRNP, hnRNP UL1 perturbation, and ChIP in HeLa cells

    PMID:22451911

    Open questions at the time
    • Mechanism coupling U7 snRNP to transcriptional machinery at the chromatin level incomplete
    • Single-lab finding
  8. 2017 Medium

    Defined how the substrate is engaged, showing SLBP stabilizes U7 snRNP binding to histone pre-mRNA in a FLASH-dependent manner.

    Evidence In vitro processing and binding assays with SLBP domain mutagenesis and human/Drosophila pulldowns

    PMID:28289156

    Open questions at the time
    • Quantitative contribution of Lsm10 to SLBP-stabilized binding not isolated
    • In vitro system may not capture full assembly context
  9. 2022 High

    Connected Lsm10/Lsm11 dosage to disease, showing co-expression rescues U7 snRNP assembly, histone processing, and neuromuscular pathology in SMA mice.

    Evidence In vivo co-expression in a mouse SMA model with assembly/processing assays, electrophysiology, and NMJ immunostaining

    PMID:36130491

    Open questions at the time
    • Causal chain from histone processing to Agrin loss at NMJs not fully mechanistic
    • Whether Lsm10 alone (vs the dimer) is sufficient not tested
  10. 2023 High

    Provided the structural basis for chaperone recognition, showing the Lsm10/Lsm11 heterodimer engages the PRMT5/MEP50/pICln methylosome through PRMT5 binding to Lsm11 without methylating Lsm10.

    Evidence Biochemical co-purification, cryo-EM structural analysis, and in vitro methylation assays

    PMID:37562960

    Open questions at the time
    • Subsequent transfer from methylosome to SMN not structurally resolved
    • Role of Lsm10 surfaces in the interface not detailed
  11. 2025 Medium

    Identified new U7 snRNA-binding factors (PTBP1, IGF2BP3, hnRNP A1) that may direct assembly of the Lsm10/Lsm11-containing Sm ring, addressing how the noncanonical Sm site is selected.

    Evidence RNA pulldown from mammalian extracts, Co-IP of hnRNP A1 with SMN, and binding competition assays

    PMID:40592581

    Open questions at the time
    • hnRNP A1 substitution for Gemin5 proposed but not reconstituted
    • Direct effect of these factors on Lsm10 incorporation not demonstrated
    • Single-lab finding

Open questions

Synthesis pass · forward-looking unresolved questions
  • The identity of the endonuclease whose cleavage site is defined by the Lsm10-containing molecular ruler, and the structural transition from methylosome handoff to the mature catalytic U7 snRNP, remain unresolved.
  • No structure of the full processing-competent U7 snRNP on substrate
  • Direct catalytic partner positioned by the ruler not defined
  • Mechanism of cell-type-specific HLB targeting unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 2 GO:0005198 structural molecule activity 2
Localization
GO:0005634 nucleus 2 GO:0005654 nucleoplasm 2
Pathway
R-HSA-8953854 Metabolism of RNA 3 R-HSA-74160 Gene expression (Transcription) 1
Partners
HNRNP A1HNRNP UL1LSM11PICLNPRMT5SMBSMD3SMN1
Complex memberships
PRMT5/MEP50/pICln methylosomeSMN complexU7 snRNP

Evidence

Reading pass · 15 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 LSM10 (Lsm10) is a novel 14 kDa Sm-like protein that replaces Sm D1 in the U7 snRNP Sm core ring; purified U7 snRNPs from HeLa cells lack Sm D1 and D2 but contain Lsm10, and its incorporation into U7 snRNPs is largely dictated by the special Sm-binding site of U7 snRNA. Biochemical fractionation and affinity purification of U7 snRNPs from HeLa cells, microsequencing of isolated polypeptides The EMBO journal High 11574479
2001 Lsm10 is enriched in Cajal bodies of the cell nucleus, co-localizing with U7 snRNA. Immunofluorescence microscopy / subcellular localization in HeLa cells The EMBO journal Medium 11574479
2003 The U7-specific Sm core containing Lsm10 (and Lsm11) is assembled by a specialized SMN complex that contains Lsm10 and Lsm11 but lacks Sm D1/D2; assembly depends on the noncanonical Sm-binding site of U7 snRNA. In vitro assembly assays, co-immunoprecipitation, biochemical reconstitution with specialized SMN complex Genes & development High 12975319
2003 Drosophila Lsm10 (dLsm10) associates with dLsm11 and Sm B but not with Sm D1 and D2, and Drosophila Lsm10 and Lsm11 can assemble into U7 snRNPs in mammalian cells, demonstrating evolutionary conservation of the unique U7 snRNP composition. Immunoprecipitation studies in Drosophila S2 cells; cross-species assembly assays in mammalian cells RNA (New York, N.Y.) Medium 14624008
2005 Lsm10 and Lsm11 associate with pICln (a subunit of the PRMT5 methylosome complex) in vitro and in vivo without receiving symmetrical dimethylarginine (sDMA) modifications, and their binding to SMN is independent of methylation activity; two separate binding sites in SMN exist for Sm/Lsm proteins. Co-immunoprecipitation in vivo and in vitro binding assays; methylation assays; SMN binding studies The Journal of biological chemistry Medium 16087681
2006 Overexpression of Lsm10 and Lsm11 increases cellular levels of U7 snRNP but has no effect on histone pre-mRNA processing; knockdown of U7 snRNP components including Lsm10 by RNAi causes reduction in cell growth and cell cycle arrest in early G1. Reporter gene assay (GFP fused to histone 3' end), RNAi knockdown, flow cytometry for cell cycle analysis Molecular and cellular biology Medium 16914750
2009 Lsm10, SmB, and SmD3 (components of the U7-specific Sm core) interact in a U7-dependent manner with the region between the cleavage site and U7-binding site in histone pre-mRNA, and function as a molecular ruler to determine the site of 3'-end cleavage. Biotin affinity pulldown of histone pre-mRNA processing complexes, UV cross-linking studies Molecular and cellular biology Medium 19470752
2009 In Drosophila, loss of Lsm10 disrupts histone pre-mRNA processing, causing production of polyadenylated histone mRNA from cryptic downstream sites; Lsm10 protein fails to accumulate in Lsm11 mutants, suggesting Lsm10-Lsm11 dimers are precursors for U7 snRNP assembly; Lsm10 and Lsm11 are necessary for localization of U7 snRNA to the histone locus body. Drosophila genetic loss-of-function (Lsm10 and Lsm11 null mutants), RT-PCR for polyadenylated histone mRNA, immunostaining, anti-trimethylguanosine immunoprecipitation RNA (New York, N.Y.) High 19620235
2009 In normal human somatic and embryonic stem cells, Lsm10-containing U7 snRNP co-localizes with p220(NPAT) and the histone gene locus in Histone Locus Bodies (HLBs); in certain cancer cell lines (HeLa S3, MCF7), this co-localization is disrupted with most Lsm10 residing in Cajal bodies instead. In situ immunofluorescence microscopy and FISH in human cell lines Journal of cellular physiology Medium 19277982
2011 In Drosophila, direct interaction between FLASH (amino acids 105–154) and dLsm11 (amino acids 1–78) is essential for histone pre-mRNA processing in vivo; a two-amino-acid mutation in dLsm11 that prevents dFLASH binding—without affecting U7 snRNP localization to the HLB—cannot rescue lethality or processing defects caused by Lsm11 null mutation. Drosophila genetic rescue experiments, in vitro binding/pulldown assays, site-directed mutagenesis, dominant-negative analysis RNA (New York, N.Y.) High 21525146
2012 Depletion of Lsm10 (a component of the U7 snRNP-specific Sm ring) by siRNA in HeLa cells results in elevated levels of replication-dependent histone mRNAs under cell cycle-arrested conditions, acting at the transcriptional level; U7 snRNP (identified via Lsm10 component) interacts with hnRNP UL1, which mediates U7 snRNP-dependent transcriptional repression of histone genes. siRNA knockdown, pulse-chase experiments, mass spectrometry of captured U7 snRNP, hnRNP UL1 knockdown/overexpression, chromatin immunoprecipitation (ChIP) Proceedings of the National Academy of Sciences of the United States of America Medium 22451911
2017 U7 snRNP (containing Lsm10/Lsm11) is recruited to histone pre-mRNA in a FLASH-dependent manner; SLBP stabilizes U7 snRNP binding via two regions (helix B of its RNA-binding domain and C-terminal region), and this stabilization requires FLASH but not polyadenylation factors. In vitro histone pre-mRNA processing and binding assays, mutagenesis of SLBP domains, pulldown assays with Drosophila and human SLBP RNA (New York, N.Y.) Medium 28289156
2022 Co-expression of U7-specific Lsm10 and Lsm11 proteins selectively enhances U7 snRNP assembly, corrects histone mRNA processing defects, and rescues key structural and functional neuromuscular pathology (NMJ denervation, decreased synaptic transmission, skeletal muscle atrophy) in SMA mice; U7 snRNP dysfunction drives selective loss of synaptic organizing protein Agrin at NMJs. Mouse SMA model (in vivo co-expression of Lsm10 and Lsm11), U7 snRNP assembly assays, histone mRNA processing assays, electrophysiology, immunostaining of NMJ Cell reports High 36130491
2023 A heterodimer of Lsm10 and Lsm11 tightly interacts with the PRMT5/MEP50/pICln methylosome complex; the interaction is mediated by PRMT5 which binds Lsm11 but does not methylate Lsm10; cryo-EM structural studies demonstrate the mode of interaction. Biochemical co-purification, cryo-EM structural analysis, in vitro methylation assays RNA (New York, N.Y.) High 37562960
2025 Two proteins, PTBP1 and IGF2BP3, bind U7 snRNA in a manner dependent on its unique Sm site and upstream CUCUUU motif; hnRNP A1 also binds U7 snRNA and interacts with SMN, suggesting it may substitute for Gemin5 in directing assembly of the U7-specific Sm ring containing Lsm10 and Lsm11. RNA pulldown/affinity purification from mammalian extracts, co-immunoprecipitation of hnRNP A1 with SMN, binding competition assays RNA (New York, N.Y.) Medium 40592581

Source papers

Stage 0 corpus · 19 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2003 Unique Sm core structure of U7 snRNPs: assembly by a specialized SMN complex and the role of a new component, Lsm11, in histone RNA processing. Genes & development 182 12975319
2001 Purified U7 snRNPs lack the Sm proteins D1 and D2 but contain Lsm10, a new 14 kDa Sm D1-like protein. The EMBO journal 138 11574479
2004 The special Sm core structure of the U7 snRNP: far-reaching significance of a small nuclear ribonucleoprotein. Cellular and molecular life sciences : CMLS 120 15526162
2011 Interaction between FLASH and Lsm11 is essential for histone pre-mRNA processing in vivo in Drosophila. RNA (New York, N.Y.) 41 21525146
2005 Toward an assembly line for U7 snRNPs: interactions of U7-specific Lsm proteins with PRMT5 and SMN complexes. The Journal of biological chemistry 37 16087681
2009 The subnuclear organization of histone gene regulatory proteins and 3' end processing factors of normal somatic and embryonic stem cells is compromised in selected human cancer cell types. Journal of cellular physiology 31 19277982
2009 The Drosophila U7 snRNP proteins Lsm10 and Lsm11 are required for histone pre-mRNA processing and play an essential role in development. RNA (New York, N.Y.) 30 19620235
2017 U7 snRNP is recruited to histone pre-mRNA in a FLASH-dependent manner by two separate regions of the stem-loop binding protein. RNA (New York, N.Y.) 29 28289156
2012 U7 small nuclear ribonucleoprotein represses histone gene transcription in cell cycle-arrested cells. Proceedings of the National Academy of Sciences of the United States of America 29 22451911
2022 SMN controls neuromuscular junction integrity through U7 snRNP. Cell reports 27 36130491
2006 ZFP100, a component of the active U7 snRNP limiting for histone pre-mRNA processing, is required for entry into S phase. Molecular and cellular biology 27 16914750
2022 Identification of LSM Family Members as Novel Unfavorable Biomarkers in Hepatocellular Carcinoma. Frontiers in oncology 24 35646684
2003 Evolutionary conservation of the U7 small nuclear ribonucleoprotein in Drosophila melanogaster. RNA (New York, N.Y.) 23 14624008
2009 Three proteins of the U7-specific Sm ring function as the molecular ruler to determine the site of 3'-end processing in mammalian histone pre-mRNA. Molecular and cellular biology 21 19470752
2019 Composition of the Survival Motor Neuron (SMN) Complex in Drosophila melanogaster. G3 (Bethesda, Md.) 17 30563832
2010 Octamer-binding factor 6 (Oct-6/Pou3f1) is induced by interferon and contributes to dsRNA-mediated transcriptional responses. BMC cell biology 16 20687925
2023 In vitro methylation of the U7 snRNP subunits Lsm11 and SmE by the PRMT5/MEP50/pICln methylosome. RNA (New York, N.Y.) 5 37562960
2025 Proteins that recognize unique features of U7 snRNA and may substitute for Gemin5 in the assembly of U7-specific Sm ring. RNA (New York, N.Y.) 0 40592581
2023 In vitro methylation of the U7 snRNP subunits Lsm11 and SmE by the PRMT5/MEP50/pICln methylosome. bioRxiv : the preprint server for biology 0 37215023

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