Affinage

SRRM2

Serine/arginine repetitive matrix protein 2 · UniProt Q9UQ35

Round 2 corrected
Length
2752 aa
Mass
299.6 kDa
Annotated
2026-04-28
60 papers in source corpus 23 papers cited in narrative 23 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SRRM2 is a large, intrinsically disordered serine/arginine-repeat protein that serves as a core scaffold of nuclear speckles and a direct participant in pre-mRNA splicing catalysis. Together with SON, SRRM2 drives nuclear speckle formation through liquid-liquid phase separation mediated by its RS domains, which form higher-order oligomers whose serine phosphorylation state tunes condensate liquidity; co-depletion of both proteins dissolves speckles and repositions associated chromatin to the nuclear periphery with acquisition of repressive marks (PMID:33095160, PMID:38381607). At the spliceosome, SRRM2 docks via its conserved cwf21 domain to the catalytic-center proteins Prp8 and Snu114, promoting the first step of splicing, and its depletion causes skipping of cassette exons with weak splice sites and short introns, with downstream consequences for pluripotency, innate immunity, mTOR–S6K signaling, and genome stability through sororin splicing (PMID:19854871, PMID:35929045, PMID:28062851, PMID:39956864). Beyond splicing, the C. elegans ortholog RSR-2 co-localizes with and modulates RNA polymerase II phosphorylation in a splicing-independent manner, and nuclear arginyl-tRNA synthetase interacts with SRRM2 to couple arginine availability to condensate dynamics and splice-site selection during inflammation (PMID:23754964, PMID:37059883).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2000 Medium

    Identification of SRRM2 as a novel RS-domain-containing RNA-binding protein established the molecular framework for subsequent studies of its dual roles in splicing and nuclear organization.

    Evidence cDNA cloning and immunoblot characterization of human and rat SRL300/SRRM2

    PMID:11004489

    Open questions at the time
    • No functional assays performed
    • Phosphorylation sites identified but kinase/substrate relationships unknown
  2. 2002 Medium

    Detection of SRRM2 in catalytically active spliceosomal C complexes placed it directly within the splicing machinery rather than being solely a nuclear speckle structural component.

    Evidence Affinity purification of native spliceosomes with tandem mass spectrometry identification

    PMID:11991638

    Open questions at the time
    • No direct binding partners within the spliceosome mapped
    • Functional requirement not tested by depletion
  3. 2003 Medium

    Mapping the physical interaction between SRRM2 and Pinin at nuclear speckles, and demonstrating a role as a HTLV-1 Tax transcriptional co-activator, revealed that SRRM2 participates in both splicing-associated complexes and transcriptional regulation.

    Evidence Yeast two-hybrid, reciprocal co-IP, siRNA knockdown with luciferase reporter assays in HEK-293 and HCE-T cells

    PMID:12941912 PMID:14578391

    Open questions at the time
    • Tax co-activation mechanism not resolved at the structural level
    • Pinin interaction domain on SRRM2 not precisely mapped
  4. 2009 High

    Biochemical and genetic studies in yeast and human cells established that SRRM2's conserved cwf21 domain docks directly to Prp8 and Snu114 at the catalytic center, positioning SRRM2 at the first step of splicing.

    Evidence Direct binding assays, chemical cross-linking, yeast genetic epistasis, and human ortholog validation

    PMID:19789211 PMID:19854871

    Open questions at the time
    • No high-resolution structural data of the cwf21–Prp8 interface
    • Catalytic contribution versus structural scaffolding role not distinguished
  5. 2013 High

    Characterization of the C. elegans ortholog RSR-2 revealed a splicing-independent function in modulating RNA polymerase II phosphorylation, broadening SRRM2's role to transcription regulation.

    Evidence ChIP-Seq, co-IP with RNAPII, quantitative proteomics, and genetic epistasis in C. elegans germline

    PMID:23754964

    Open questions at the time
    • Whether RNAPII phosphorylation modulation is conserved in mammals remains untested in this study
    • Kinase or phosphatase intermediary not identified
  6. 2015 Medium

    A germline SRRM2 missense mutation (S346F) co-segregating with papillary thyroid carcinoma was shown to cause widespread alternative splicing changes, providing the first genetic evidence that SRRM2 variants alter splicing of specific exon subsets in human disease.

    Evidence Whole-exome sequencing, RNA-Seq with RT-PCR validation in carrier leukocytes

    PMID:26135620

    Open questions at the time
    • Causal mechanism linking S346F to splicing dysregulation not determined
    • No functional rescue experiment performed
  7. 2017 Medium

    Discovery that cactin/DHX8/SRRM2 complexes are required for faithful splicing of the sororin pre-mRNA linked SRRM2 splicing function to genome stability and chromosome segregation.

    Evidence Co-IP, siRNA depletion with chromosome segregation phenotyping, RNA-Seq splicing analysis

    PMID:28062851

    Open questions at the time
    • Stoichiometry and assembly order of the cactin–DHX8–SRRM2 complex unknown
    • Whether SRRM2 is required for all cactin-dependent splicing events untested
  8. 2020 High

    Demonstration that the SC35 antibody targets SRRM2 (not SRSF2) and that co-depletion of SRRM2 and SON dissolves nuclear speckles established these two proteins as the essential scaffolds of nuclear speckle architecture.

    Evidence IP-MS antibody characterization, siRNA co-depletion, CRISPR deletion of SRRM2 IDRs, fluorescence microscopy

    PMID:33095160

    Open questions at the time
    • Relative contribution of SRRM2 versus SON to speckle nucleation not resolved
    • Whether speckle dissolution fully explains splicing changes upon depletion unclear
  9. 2022 High

    In vitro reconstitution and endogenous tagging showed SRRM2 undergoes bona fide liquid-liquid phase separation that organizes nuclear speckles throughout the cell cycle, while RNA-Seq defined its preferred substrates as cassette exons with weak splice sites.

    Evidence EGFP knock-in live-cell imaging, in vitro LLPS assays, RNA-Seq after depletion, cell viability assays in THP-1 cells

    PMID:35929045

    Open questions at the time
    • Molecular determinants distinguishing SRRM2-regulated from SON-regulated exons not fully defined
    • Phase separation parameters under physiological crowding conditions not measured
  10. 2023 High

    The interaction between nuclear arginyl-tRNA synthetase and SRRM2 revealed a metabolic sensing axis where arginine depletion during inflammation alters SRRM2 condensate dynamics and splice-site selection, coupling amino acid metabolism to immune-relevant splicing.

    Evidence Reciprocal co-IP, co-localization imaging, RNA-Seq splice-site analysis, immunopeptidome and metabolic assays

    PMID:37059883

    Open questions at the time
    • Direct biochemical mechanism by which ArgRS modulates SRRM2 phase behavior unknown
    • Whether other aminoacyl-tRNA synthetases regulate speckle components untested
  11. 2024 High

    Dissection of SRRM2 and SON as forming immiscible multiphases within speckles, with RS domain oligomerization driving SRRM2 phase separation and serine residues tuning liquidity, provided a molecular mechanism for speckle subcompartmentalization and demonstrated functional independence of the two scaffolds in splicing regulation.

    Evidence FRAP, RS domain mutagenesis and synthetic module replacement, in vitro LLPS, individual knockdown RNA-Seq

    PMID:38381607

    Open questions at the time
    • How immiscible SRRM2 and SON phases coordinate during co-transcriptional splicing is unknown
    • In vivo consequences of synthetic oligomerizable domain replacement not tested in animal models
  12. 2024 Medium

    Srrm2 haploinsufficiency in mouse ESCs disrupts the balance between naive and formative pluripotency via specific alternative splicing changes, establishing dosage sensitivity of SRRM2 in cell fate decisions.

    Evidence Srrm2+/- mouse ESC model, RNA-Seq splicing and expression analysis, pluripotency marker immunostaining

    PMID:38656788

    Open questions at the time
    • Whether splicing changes are primary cause or secondary consequence of pluripotency loss requires rescue experiments
    • Human ESC validation not performed
  13. 2025 Medium

    SRRM2 was shown to modulate mTOR–S6K signaling in colorectal cancer by regulating S6K2 alternative splicing and S6K1 protein stability via the E3 ligase WWP2, linking its splicing scaffold function to oncogenic signaling.

    Evidence siRNA/overexpression, RNA-Seq splicing analysis, ubiquitination assays, xenograft models

    PMID:39956864

    Open questions at the time
    • Whether SRRM2–WWP2 interaction is direct remains unresolved
    • Generalizability beyond colorectal cancer untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the high-resolution structure of SRRM2 within the spliceosome, the precise mechanism by which RS domain phosphorylation (by kinases such as CLK3 and TAOK2) regulates speckle dynamics and splicing target selection, and whether SRRM2 haploinsufficiency underlies neurodevelopmental or neurodegenerative disease in humans.
  • No atomic-resolution structure of SRRM2 in any complex
  • Kinase–substrate relationships for SRRM2 phosphorylation sites lack direct in vitro validation
  • Causal role of SRRM2 variants in neuropsychiatric and neurodegenerative disease awaits clinical genetic confirmation

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 3 GO:0003723 RNA binding 2
Localization
GO:0005654 nucleoplasm 4 GO:0005634 nucleus 3
Pathway
R-HSA-8953854 Metabolism of RNA 8 R-HSA-4839726 Chromatin organization 2 R-HSA-74160 Gene expression (Transcription) 2
Partners
ACIN1CACTINDHX8PNNPRP8RARS1SNU114SON
Complex memberships
cactin–DHX8–SRRM2 complexnuclear speckle (SON/SRRM2 scaffold)spliceosomal C complex

Evidence

Reading pass · 23 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 SRRM2 (termed SRL300) was cloned and characterized as a novel RNA-binding protein containing a unique RNA-binding region and two large RS (arginine-serine repeat) domains with multiple phosphorylation sites, expressed in both human and rat cells. cDNA cloning and characterization; protein detection by immunoblot Biochimica et biophysica acta Medium 11004489
2002 SRRM2 (SRm300) was identified as a component of catalytically active spliceosomal C complexes containing splicing intermediates, detected by tandem mass spectrometry in affinity-purified native spliceosomes. Affinity purification of native spliceosomes followed by tandem mass spectrometry RNA (New York, N.Y.) Medium 11991638
2003 SRRM2 (SRm300) physically interacts with Pinin (Pnn/DRS/memA) via Pnn's polyserine/RS motif and co-localizes with Pnn and SRp75 in nuclear speckles in corneal epithelial cells; these proteins co-immunoprecipitate and form a multiprotein complex associated with pre-mRNA splicing machinery. Yeast two-hybrid, co-immunoprecipitation, co-transfection with immunostaining in HCE-T and HEK-293 cells Investigative ophthalmology & visual science Medium 14578391
2003 SRRM2 (TAXREB803/SRL300) functions as a transcriptional co-activator for HTLV-1 Tax protein; it binds to the Tax responsive element (TxRE) in a GC-rich sequence-dependent manner, enhances Tax-dependent transcription and CREB binding to TxRE, and physically interacts with Tax as shown by co-immunoprecipitation. Knockdown of endogenous SRRM2 by siRNA dramatically reduces Tax transactivation of the HTLV-1 LTR. Yeast two-hybrid, co-immunoprecipitation, indirect immunofluorescence, siRNA knockdown with luciferase reporter assay Journal of virology Medium 12941912
2009 Yeast Cwc21p (ortholog of human SRm300/SRRM2) binds directly to the splicing factors Prp8p and Snu114p, docking it to U5 snRNP proteins, and is the first NTC-related protein known to interact directly with U5 snRNP. The conserved cwf21 domain in Cwc21p is identified as the Prp8p binding site by chemical cross-linking. Genetic interactions with Isy1p place Cwc21p at or prior to the first catalytic step of splicing. Importantly, human SRm300 was shown to be a functional ortholog of Cwc21p, also interacting directly with Prp8p and Snu114p, placing SRRM2 at the catalytic center of the human spliceosome. Direct binding assays, chemical cross-linking, yeast two-hybrid, genetic epistasis, proteomic techniques including tandem affinity purification RNA (New York, N.Y.) High 19854871
2009 Cwc21 (yeast ortholog of SRm300/SRRM2) shows strong genetic, physical, and functional interactions with Isy1 (a protein implicated in the first catalytic step of splicing and splicing fidelity), and genetic interaction mapping supports multiple roles for Cwc21/SRm300 in the formation and function of splicing complexes including activation of splicing. Quantitative genetic interaction mapping (E-MAP), mass spectrometry of tandem affinity-purified complexes, microarray profiling RNA (New York, N.Y.) High 19789211 19854871
2013 RSR-2 (C. elegans ortholog of SRRM2) is essential for viability and lies within the germline sex determination pathway by genetic epistasis. RSR-2 co-precipitates with chromatin and co-localizes with RNA Polymerase II (RNAPII) in germline nuclei, with a ChIP-Seq profile mirroring that of RNAPII. RSR-2 interacts with RNAPII and affects RNAPII phosphorylation states in a splicing-independent manner, and its strongest proteomic interactors are PRP-8 and PRP-19. This reveals a transcriptional function for SRRM2/RSR-2 beyond splicing. RNAi/mutant genetic epistasis, ChIP-Seq, co-immunoprecipitation, quantitative proteomics (mass spectrometry), immunostaining PLoS genetics High 23754964
2015 A germline missense mutation in SRRM2 (S346F) co-segregates with papillary thyroid carcinoma and causes significant differences in alternative splicing affecting 1,642 exons in leukocytes from mutation carriers, with a net higher ratio of exon inclusion, establishing that SRRM2 S346F alters alternative splicing of downstream target genes. Whole exome sequencing, haplotype analysis, RNA-Seq comparison of mutation carriers vs. controls, RT-PCR validation of 7 exons Scientific reports Medium 26135620
2017 Human cactin physically and functionally interacts with SRRM2 (and DHX8); cactin depletion leads to premature sister chromatid separation and genome instability caused by incomplete splicing of the sororin (CDCA5) pre-mRNA, establishing that cellular complexes comprising cactin, DHX8, and SRRM2 sustain pre-mRNA splicing fidelity for specific targets required for chromosome segregation. Co-immunoprecipitation, siRNA knockdown with defined phenotypic readouts (chromosome separation, genome instability), RNA-Seq splicing analysis Journal of cell science Medium 28062851
2020 The SC35 monoclonal antibody (widely used to mark nuclear speckles) was found to primarily target SRRM2, not SRSF2/SC35 as previously believed. Co-depletion of SON and SRRM2, or depletion of SON in cells where the intrinsically disordered regions (IDRs) of SRRM2 are genetically deleted, leads to near-complete dissolution of nuclear speckles, establishing SON and SRRM2 as the core scaffold proteins required for nuclear speckle formation. Antibody characterization (immunoprecipitation-MS), siRNA co-depletion, CRISPR-mediated genetic deletion of SRRM2 IDRs, fluorescence microscopy of nuclear speckles eLife High 33095160
2022 SRRM2 forms biomolecular condensates via liquid-liquid phase separation (LLPS), displaying spherical shape, dynamic rearrangement, coalescence, and concentration-dependent behavior confirmed by in vitro experiments. SRRM2 organizes nuclear speckles throughout the cell cycle. SRRM2 deficiency causes skipping of cassette exons with short introns and weak splice sites, and in THP-1 cells compromises viability, upregulates differentiation markers, and sensitizes cells to anti-leukemia drugs. SRRM2 regulates FES and MUC1 splice isoforms linked to innate immunity and oncogenic properties. EGFP-SRRM2 knock-in HEK293T cells, live-cell imaging, in vitro phase separation assays, RNA-Seq after SRRM2 depletion, cell viability assays, flow cytometry Nucleic acids research High 35929045
2023 Nuclear arginyl-tRNA synthetase (ArgRS) physically interacts and co-localizes with SRRM2; during inflammation, arginine depletion reduces nuclear ArgRS levels, which correlates with changes in condensate-like nuclear trafficking of SRRM2 and altered splice-site usage in specific genes, resulting in different protein isoforms that alter cellular metabolism and peptide presentation to immune cells. Co-immunoprecipitation, co-localization imaging, siRNA depletion, RNA-Seq splice-site analysis, metabolic and immunopeptidome assays Nature cell biology High 37059883
2024 SRRM2 and SON form immiscible multiphases within nuclear speckles and are functionally independent, each regulating distinct subsets of alternative splicing targets. SRRM2 forms multicomponent liquid phases through homotypic interaction and heterotypic protein-RNA complex coacervation-driven phase separation. The serine/arginine-rich (RS) domains of SRRM2 form higher-order oligomers required for phase separation, and the serine residues within RS domains fine-tune nuclear speckle liquidity. RS domains can be functionally replaced by synthetic oligomerizable modules. Live-cell imaging, FRAP, in vitro phase separation assays, RS domain mutagenesis and synthetic module replacement, RNA-Seq of SRRM2 and SON individual knockdowns Cell reports High 38381607
2024 SRRM2 modulates Srrm2 dosage is critical for maintaining embryonic stem cell pluripotency; Srrm2 heterozygosity in mouse ESCs promotes loss of stemness with coexistence of naive and formative pluripotency markers. The earliest effects are specific alternative splicing changes on a small number of genes, followed by expression changes in metabolism and differentiation-related genes including SRF-regulated targets. Srrm2 heterozygous mouse ESC model, RNAi knockdown, RNA-Seq, splicing analysis, pluripotency marker immunostaining Biology open Medium 38656788
2025 SRRM2 modulates the levels of both S6K1 and S6K2 to activate the mTOR-S6K pathway in colorectal cancer cells. Mechanistically, SRRM2 facilitates S6K2 expression by regulating alternative splicing of the S6K2 pre-mRNA, and enhances S6K1 protein stability by regulating the E3 ubiquitin ligase WWP2. SRRM2 knockdown or overexpression modulates CRC cell growth in vitro and in vivo. siRNA knockdown and overexpression, RNA-Seq splicing analysis, protein stability assays, ubiquitination assays, xenograft mouse models Oncogene Medium 39956864
2025 A point mutation in SRRM2 (identified in an ALS family) causes loss of a specific protein-protein interaction between SRRM2 and the splicing factor ACIN1, leading to widespread differential gene expression converging on dysregulation of synapse-associated pathways, identifying SRRM2 as a novel ALS risk factor. Endogenous point mutation knock-in cell line, co-immunoprecipitation, RNA-Seq transcriptome analysis bioRxivpreprint Medium bio_10.1101_2025.09.11.675713
2024 Srrm2+/- heterozygous mice display large-scale changes in gene expression in neuronal and glial cells, reduction of key postsynaptic proteins including the SynGAP-γ isoform, abnormal splicing and elevated expression of Agap3 (a SynGAP interactor), reduced numbers of oligodendrocytes with decreased myelin-related mRNAs and proteins, and behavioral/EEG abnormalities including reduced sleep spindles phenocopying schizophrenia. Srrm2+/- mouse model, RNA-Seq in multiple brain regions, proteomics, immunostaining, EEG, behavioral testing bioRxivpreprint Medium bio_10.1101_2024.10.10.617460
2025 Upon simultaneous dTAG-mediated depletion of SON and SRRM2, specific genomic regions (SWING domains) relocate to the nuclear periphery and acquire repressive histone marks (H3K9me3) with transcriptional downregulation of developmental pathway genes, establishing nuclear speckles (scaffolded by SON and SRRM2) as organizers of active chromatin that oppose nuclear lamina-associated gene repression. Rapid dTAG-mediated co-depletion of SON and SRRM2, Hi-C/3D genomics, ChIP-Seq (H3K9me3), RNA-Seq, patient-derived cell analysis bioRxivpreprint Medium bio_10.1101_2025.10.01.679801
2025 SRRM2 (and SRRM1) are identified as potential direct phosphorylation substrates of the nuclear speckle-localized kinase TAOK2 by cellular and biochemical phosphoproteomics; TAOK2 knockdown perturbs nearly all speckle-resident SR proteins and disrupts speckle integrity and speckle-localized splicing, suggesting that TAOK2-mediated phosphorylation of SRRM1/2 plays a structural maintenance role at nuclear speckles. siRNA knockdown, cellular and biochemical phosphoproteomics, RNA-Seq (alternative splicing analysis), immunofluorescence of speckle-resident proteins bioRxivpreprint Low bio_10.1101_2025.09.29.679379
2024 The intrinsically disordered region (IDR) of SRRM2 is required for enlargement of nuclear speckles in the presence of the HIV capsid, and HIV-induced CPSF6 puncta fuse with nuclear speckles via the IDR of SRRM2. Genetic manipulation and depletion experiments, live-cell imaging of SRRM2 IDR mutants, HIV infection assays bioRxivpreprint Low bio_10.1101_2024.10.06.616889
2025 Downregulation of SRRM2 disrupts nuclear speckle integrity and promotes TDP-43 mislocalization from the nucleus to the cytoplasm and loss of TDP-43 splicing function, linking SRRM2-dependent speckle maintenance to TDP-43 pathology relevant to ALS/FTLD. APEX2 proximity labeling, mass spectrometry interactome, siRNA knockdown of SRRM2, TDP-43 localization imaging, cryptic exon splicing assay bioRxivpreprint Medium bio_10.1101_2025.04.07.646890
2024 In senescent cells, SRRM2 is repurposed to cluster CTCF into senescence-induced clusters (SICCs) on nuclear speckles, a process dependent on SRRM2's RNA-binding domain. This CTCF clustering rewires chromatin positioning and is functionally required to sustain the senescence-specific alternative splicing program, as SICC disruption fully reverts alternative splicing patterns. Super-resolution imaging, 3D genomics, functional splicing assays, SRRM2 domain deletion experiments, siRNA knockdown with chromatin and splicing readouts bioRxivpreprint Medium bio_10.1101_2024.07.16.603680
2025 Polyphosphate (polyP) directly interacts with the nuclear speckle core component SRRM2; polyP depletion disrupts nuclear speckle organization and releases splicing factors into the nucleoplasm. PolyP acts as a physiological inhibitor of CLK3 kinase, preventing CLK3-mediated phosphorylation of SR proteins and thereby maintaining nuclear speckle stability. PolyP depletion increases exon inclusion particularly in long multi-exon genes. BAR (Biotinylation by Antibody Recognition) proximity labeling, polyP depletion, RNA-Seq splicing analysis, CLK3 kinase inhibition assays, nuclear speckle imaging bioRxivpreprint Low bio_10.1101_2025.01.15.633116

Source papers

Stage 0 corpus · 60 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2009 Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science (New York, N.Y.) 3312 19608861
2006 Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell 2861 17081983
2012 Insights into RNA biology from an atlas of mammalian mRNA-binding proteins. Cell 1718 22658674
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2006 A probability-based approach for high-throughput protein phosphorylation analysis and site localization. Nature biotechnology 1336 16964243
2009 Defining the human deubiquitinating enzyme interaction landscape. Cell 1282 19615732
2004 Large-scale characterization of HeLa cell nuclear phosphoproteins. Proceedings of the National Academy of Sciences of the United States of America 1159 15302935
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2012 The mRNA-bound proteome and its global occupancy profile on protein-coding transcripts. Molecular cell 973 22681889
2018 VIRMA mediates preferential m6A mRNA methylation in 3'UTR and near stop codon and associates with alternative polyadenylation. Cell discovery 829 29507755
2007 Large-scale mapping of human protein-protein interactions by mass spectrometry. Molecular systems biology 733 17353931
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2012 A census of human soluble protein complexes. Cell 689 22939629
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2011 Global landscape of HIV-human protein complexes. Nature 593 22190034
2018 High-Density Proximity Mapping Reveals the Subcellular Organization of mRNA-Associated Granules and Bodies. Molecular cell 580 29395067
2017 Anticancer sulfonamides target splicing by inducing RBM39 degradation via recruitment to DCAF15. Science (New York, N.Y.) 533 28302793
2020 SARS-CoV-2 Disrupts Splicing, Translation, and Protein Trafficking to Suppress Host Defenses. Cell 449 33080218
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
2015 Panorama of ancient metazoan macromolecular complexes. Nature 407 26344197
2004 Proteomic, functional, and domain-based analysis of in vivo 14-3-3 binding proteins involved in cytoskeletal regulation and cellular organization. Current biology : CB 386 15324660
2007 Functional specialization of beta-arrestin interactions revealed by proteomic analysis. Proceedings of the National Academy of Sciences of the United States of America 360 17620599
2021 A proximity-dependent biotinylation map of a human cell. Nature 339 34079125
2012 Interpreting cancer genomes using systematic host network perturbations by tumour virus proteins. Nature 319 22810586
2012 Dynamic protein-protein interaction wiring of the human spliceosome. Molecular cell 318 22365833
2010 Dynamics of cullin-RING ubiquitin ligase network revealed by systematic quantitative proteomics. Cell 318 21145461
2002 Purification and characterization of native spliceosomes suitable for three-dimensional structural analysis. RNA (New York, N.Y.) 301 11991638
2020 SON and SRRM2 are essential for nuclear speckle formation. eLife 197 33095160
2010 SRRM2, a potential blood biomarker revealing high alternative splicing in Parkinson's disease. PloS one 94 20161708
2022 SRRM2 organizes splicing condensates to regulate alternative splicing. Nucleic acids research 82 35929045
2015 A germline mutation in SRRM2, a splicing factor gene, is implicated in papillary thyroid carcinoma predisposition. Scientific reports 80 26135620
2021 Pathological tau drives ectopic nuclear speckle scaffold protein SRRM2 accumulation in neuron cytoplasm in Alzheimer's disease. Acta neuropathologica communications 52 34187600
2003 Pinin/DRS/memA interacts with SRp75, SRm300 and SRrp130 in corneal epithelial cells. Investigative ophthalmology & visual science 52 14578391
2009 Physical and genetic interactions of yeast Cwc21p, an ortholog of human SRm300/SRRM2, suggest a role at the catalytic center of the spliceosome. RNA (New York, N.Y.) 46 19854871
2022 Loss-of-function variants in SRRM2 cause a neurodevelopmental disorder. Genetics in medicine : official journal of the American College of Medical Genetics 36 35567594
2024 SRRM2 phase separation drives assembly of nuclear speckle subcompartments. Cell reports 32 38381607
2009 A systematic characterization of Cwc21, the yeast ortholog of the human spliceosomal protein SRm300. RNA (New York, N.Y.) 29 19789211
2019 Silencing of long noncoding RNA SRRM2-AS exerts suppressive effects on angiogenesis in nasopharyngeal carcinoma via activating MYLK-mediated cGMP-PKG signaling pathway. Journal of cellular physiology 28 31742692
2023 Arg-tRNA synthetase links inflammatory metabolism to RNA splicing and nuclear trafficking via SRRM2. Nature cell biology 27 37059883
2020 A compound downregulation of SRRM2 and miR-27a-3p with upregulation of miR-27b-3p in PBMCs of Parkinson's patients is associated with the early stage onset of disease. PloS one 24 33171483
2017 Human cactin interacts with DHX8 and SRRM2 to assure efficient pre-mRNA splicing and sister chromatid cohesion. Journal of cell science 21 28062851
2013 RSR-2, the Caenorhabditis elegans ortholog of human spliceosomal component SRm300/SRRM2, regulates development by influencing the transcriptional machinery. PLoS genetics 13 23754964
2003 SR-related protein TAXREB803/SRL300 is an important cellular factor for the transactivational function of human T-cell lymphotropic virus type 1 Tax. Journal of virology 7 12941912
2000 Cloning and characterization of a novel RNA-binding protein SRL300 with RS domains. Biochimica et biophysica acta 7 11004489
2023 Familial and genetic association with neurodevelopmental disorders caused by a heterozygous variant in the SRRM2 gene. Frontiers in endocrinology 6 37621647
2023 A Palindrome-Like Structure on 16p13.3 Is Associated with the Formation of Complex Structural Variations and SRRM2 Haploinsufficiency. Human mutation 6 40225164
2024 SRRM2 may be a potential biomarker and immunotherapy target for multiple myeloma: a real-world study based on flow cytometry detection. Clinical and experimental medicine 5 38289482
2024 SRRM2 splicing factor modulates cell fate in early development. Biology open 4 38656788
2024 The Nuclear Speckles Protein SRRM2 Is Exposed on the Surface of Cancer Cells. Cells 4 39329747
2025 Rare SRRM2 mutation in neurodevelopmental disorders involving hyperphagia triggering severe obesity and other complication. Frontiers in medicine 3 40046925
2026 D e novo SRRM2 variants in neuroendocrine cell hyperplasia of infancy and persistent tachypnoea of infancy. The European respiratory journal 2 40967764
2025 LINC00426 promotes the progression of atherosclerosis by regulating miR-873-5p/SRRM2 axis. Cytokine 1 40233646
2025 Neurodevelopmental disorder and juvenile-onset tics associated with microdeletion of the SRRM2 gene. Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology 1 40545495
2022 Effect of GATAD1 regulating the SRRM2 gene on recurrence of thyroid tumor and its molecular mechanism. Gland surgery 1 36654960
2026 Long noncoding RNA SRRM2-AS1 mediates coronary artery damage in Kawasaki disease by promoting endothelial-to-mesenchymal transition. Clinical and experimental medicine 0 41731159
2025 The splicing factor SRRM2 modulates two S6K kinases to promote colorectal cancer growth. Oncogene 0 39956864
2025 The impact of SRRM2-AS1 in ovarian cancer: a comprehensive analysis based on pan-cancer and in vitro validation. Discover oncology 0 40515981