| 1999 |
SRm160/300 splicing coactivator is required for a purine-rich exonic splicing enhancer (ESE) to promote splicing of a Drosophila doublesex pre-mRNA. SRm160/300 independently interacts with U2 snRNP and with a human homolog of Transformer 2 (which binds purine-rich ESEs), suggesting it bridges ESE-bound activators with the snRNP spliceosome machinery. |
In vitro splicing assays with immunodepletion, co-immunoprecipitation of SRm160/300 with U2 snRNP and Tra2 homolog |
Proceedings of the National Academy of Sciences of the United States of America |
High |
10339552
|
| 2000 |
SRm160 is the more critical subunit of the SRm160/300 coactivator for splicing of SRm160/300-dependent pre-mRNAs. Specific depletion of SRm300 does not prevent splicing, whereas addition of recombinant SRm160 alone to SRm160/300-depleted reactions specifically activates splicing. |
Specific immunodepletion of SRm300 from splicing extracts; rescue with recombinant SRm160; cDNA isolation and sequence analysis of SRm300 |
RNA (New York, N.Y.) |
High |
10668804
|
| 2001 |
SRm160 functions as a general splicing coactivator by interacting with multiple SR family proteins bound to diverse ESE sequences. Multiple SR family and SR-related proteins co-immunoprecipitate specifically with SRm160 under low-salt conditions. Genetic epistasis in C. elegans shows that simultaneous RNAi of CeSRm160 and any individual CeSR family gene produces unfertilized oocytes, demonstrating critical functional interactions in vivo. |
Co-immunoprecipitation of SR proteins with SRm160; RNA interference (RNAi) genetic epistasis in C. elegans; in vitro splicing with randomized ESE sequences |
Current biology : CB |
High |
11747818
|
| 2002 |
SRm160 participates in mRNA 3'-end formation: overexpression promotes 3'-end cleavage in vivo and in vitro. At high levels, SRm160 activates 3'-end cleavage and cytoplasmic accumulation of unspliced pre-mRNAs, uncoupling the splicing requirement for 3'-end formation and nuclear export. SRm160 associates specifically with the cleavage polyadenylation specificity factor (CPSF) and stimulates cleavage of splicing-active pre-mRNAs more efficiently than splicing-inactive ones. |
In vivo overexpression assays; in vitro 3'-end cleavage assays; co-immunoprecipitation of SRm160 with CPSF |
Molecular and cellular biology |
High |
11739730
|
| 2003 |
SRm160 is associated with the nuclear matrix and co-immunoprecipitates with TLS/FUS along with splicing factors PTB (hnRNPI) and SR proteins (SC35, SRp75), suggesting SRm160 participates in spliceosome assembly within the nuclear matrix context. |
Co-immunoprecipitation from nuclear extracts; co-immunolocalization; splicing assays with TLS/FUS-immunodepleted extracts |
Experimental cell research |
Medium |
12581738
|
| 2003 |
SRm160 contains two contiguous domains (amino acids 300–350 and 351–688) that independently target it to nuclear matrix sites at splicing speckled domains. The N-terminal domain localizes SRm160 to the nuclear lamina near sites where mRNA exits the nucleus. These domains were identified as the spatial targeting and nuclear matrix binding domains. |
Fluorescence microscopy of FLAG- and EGFP-tagged deletion mutant proteins transfected into cells; nuclear matrix binding assays |
Proceedings of the National Academy of Sciences of the United States of America |
Medium |
12624182
|
| 2003 |
SRm160 stimulates 3'-end cleavage independently of its association with the exon junction complex (EJC). EJC components RNPS1, REF, UAP56, and Y14 interact with SRm160, but only SRm160 and RNPS1 stimulate 3'-end cleavage when tethered to transcripts. Assembly of an EJC adjacent to the cleavage/polyadenylation signal in vitro did not significantly affect cleavage efficiency. In C. elegans, simultaneous RNAi of SRm160 and cleavage factor CstF-50 caused late embryonic arrest, demonstrating an evolutionarily conserved functional interaction between SRm160 and the 3'-end cleavage machinery. |
In vitro tethered-function assays; in vitro 3'-end cleavage assays with EJC assembly; RNAi epistasis in C. elegans |
The Journal of biological chemistry |
High |
12944400
|
| 2004 |
SRm160 has ATP-dependent nuclear mobility at splicing speckled domains, revealed by in vitro FRAP in digitonin-permeabilized cells. Both EGFP-labeled and endogenous SRm160 are released from speckle sites by an ATP-dependent mechanism, suggesting SRm160-containing RNA export complexes (but not splicing complexes) have ATP-regulated release. In contrast, SRm300 remains immobile after ATP supplementation. |
In vitro FRAP (fluorescence recovery after photobleaching) in digitonin-permeabilized cells; comparison of EGFP-SRm160, endogenous SRm160, RNPS1, and SRm300 mobility |
The Journal of cell biology |
Medium |
15024032
|
| 2005 |
SRm160-containing complexes are associated with cohesin subunits SMC1alpha, SMC3, RAD21, and SA2. Gradient fractionation revealed two predominant SRm160 complexes: one enriched in splicing components and another enriched in cohesin subunits. Co-immunoprecipitation, co-localization, and combinatorial RNAi in C. elegans support conserved functional interactions between SRm160 and cohesin. SRm160's N-terminal PWI domain mediates its 3'-end processing stimulatory activity. |
Immunoaffinity purification + tandem mass spectrometry (gel-free); gradient fractionation; co-immunoprecipitation; co-localization; combinatorial RNAi in C. elegans |
The Journal of biological chemistry |
High |
16159877
|
| 2006 |
SRm160 regulates CD44 alternative splicing in a Ras-dependent manner: overexpression of SRm160 stimulates inclusion of CD44 variable exon 5 (v5) when Ras is activated, while siRNA-mediated silencing of SRm160 reduces v5 inclusion. SRm160 co-immunoprecipitates with Sam68, a protein that also stimulates v5 inclusion in a Ras-dependent manner, indicating these two proteins interact to regulate CD44 splicing. siRNA depletion of SRm160 reduces CD44 isoform levels and decreases tumor cell invasiveness. |
siRNA knockdown; overexpression; co-immunoprecipitation (SRm160 with Sam68); RT-PCR splicing assays; invasion assays |
Molecular and cellular biology |
High |
16354706
|
| 2014 |
In Drosophila, SRm160 is phosphorylated in vitro by the LAMMER kinase DOA, and DOA kinase alleles suppress overexpression phenotypes of SRm160 in the eye while enhancing genital disc phenotypes, indicating DOA-mediated phosphorylation modifies SRm160 activity. SRm160 overexpression causes apoptosis in the Drosophila eye and is required for somatic sex determination. SRm160 protein is concentrated in nuclei of precellular embryos but is rapidly excluded or degraded upon cellularization. |
In vitro kinase assay (DOA phosphorylates SRm160); genetic epistasis (Doa alleles modifying SRm160 overexpression/loss-of-function phenotypes); immunofluorescence localization in embryos |
Genetics |
Medium |
24907259
|
| 2017 |
In Drosophila, SRm160 is required in pacemaker neurons for proper circadian oscillations. Reduced SRm160 in adult pacemaker neurons impairs locomotor circadian rhythms and markedly reduces period (per) mRNA levels. The arrhythmicity is rescued by a fully spliced per construct but not by an extra copy of the endogenous per locus, demonstrating that SRm160 positively regulates per levels in a splicing-dependent manner. |
Tissue-specific RNAi knockdown in pacemaker neurons; genetic rescue with spliced vs. unspliced per constructs; behavioral assays; neuropeptide immunostaining (PDF/PIGMENT DISPERSING FACTOR) |
Genetics |
Medium |
28801530
|
| 2019 |
SRm160 preferentially binds to exonic trinucleotide repeats GCA and AAC, as identified by HITS-CLIP in Drosophila sex-specific cell lines (S2 male, Kc female). Binding was validated by in vitro gel-shift assays and in vivo minigene splicing assays. SRm160 regulates alternative splicing of the sex-determination factor transformer, and 492 differential binding sites between male and female cells were identified, enriched for splicing factor transcripts. |
HITS-CLIP (high-throughput sequencing of RNA isolated by crosslinking immunoprecipitation); in vitro gel-shift assay; minigene splicing assays; fly mutant analysis |
Journal of molecular cell biology |
Medium |
29750417
|
| 2025 |
SRRM1 promotes an alternative splicing program favoring oncogenic isoforms including NUMB exon 9, identified in a genome-wide CRISPR screen. SRRM1 and SRSF11 share common protein interactors, RNA targets, and oncogenic splicing effects on targets including CD44, MKNK2, ECT2, DIAPH1, KAT5, TCF7L2, FOXM1, and TBX3. Loss of SRRM1 reduces Cyclin D1, Notum, and PRDX2 expression and decreases proliferation, colony formation, and invasion in colorectal and lung cancer cells. |
Genome-wide CRISPR screen with NUMB exon 9 splicing reporter; siRNA/shRNA knockdown; proteomics for shared interactors; RNA-seq for splicing targets; cell proliferation, colony formation, and invasion assays |
bioRxivpreprint |
Medium |
bio_10.1101_2025.08.20.671097
|
| 2025 |
SRRM1 (and SRRM2) are potential direct phosphorylation targets of the nuclear speckle-localized kinase TAOK2, as revealed by phosphoproteomics. TAOK2 knockdown perturbs nearly all speckle-resident SR-rich proteins while leaving hnRNPs unperturbed, suggesting SRRM1/2 phosphorylation by TAOK2 plays a structural maintenance role at nuclear speckles that impacts SR protein-driven exon inclusion. |
Phosphoproteomics after siRNA knockdown of TAOK2; siRNA knockdown functional readouts (alternative splicing, export, transcript abundance); nuclear speckle imaging |
bioRxivpreprint |
Low |
bio_10.1101_2025.09.29.679379
|
| 2025 |
Heterozygous truncating variants in SRRM1 (introduced via CRISPR-Cas9) cause impaired proliferation, migration, and neurite outgrowth in SKNBE2 neuronal cells differentiated in vitro. Pan-neuronal knockdown of Drosophila Srrm1 reduces viability, and motoneuronal knockdown impairs neurological function, establishing a role for SRRM1 in nervous system development. |
CRISPR-Cas9 introduction of truncating variants; neuronal differentiation assays; cell proliferation, migration, and neurite morphology quantification; Drosophila pan-neuronal and motoneuronal RNAi knockdown with viability and locomotion assays |
European journal of human genetics : EJHG |
Medium |
41145827
|