| 2018 |
Upon glucose intake, SRSF5 protein is stabilized through Tip60-mediated acetylation on K125, which antagonizes Smurf1-mediated ubiquitylation on the same lysine. Upon glucose starvation, SRSF5 is deacetylated by HDAC1 and ubiquitylated by Smurf1 on K125, leading to proteasomal degradation. Stabilized SRSF5 promotes alternative splicing of CCAR1 to produce the CCAR1S isoform, which enhances glucose consumption and acetyl-CoA production to promote tumor growth. |
In vitro acetylation/ubiquitylation assays, site-directed mutagenesis (K125), Co-IP, RNAi knockdown, overexpression in cell lines and xenograft models |
Nature communications |
High |
29942010
|
| 2021 |
CLK1 phosphorylates SRSF5 at Ser250, and this phosphorylation inhibits METTL14 exon10 skipping while promoting Cyclin L2 exon6.3 skipping in pancreatic cancer cells, thereby promoting tumor growth and metastasis and regulating m6A methylation. |
Phosphorylation mass spectrometry identifying SRSF5-Ser250 as phosphorylation site, transcriptome sequencing, RIP assays, RNA pulldown, CLIP-qPCR, in vitro and in vivo functional assays |
Journal of hematology & oncology |
High |
33849617
|
| 2012 |
SRSF5 affects alternative splicing of Mcl-1 pre-mRNA in MCF-7 breast cancer cells, influencing the balance between pro-apoptotic Mcl-1(S) and anti-apoptotic Mcl-1(L) isoforms. |
RNAi knockdown of SRSF5 in MCF-7 cells with RT-PCR analysis of Mcl-1 splice isoform ratios |
PloS one |
Medium |
23284704
|
| 2018 |
SRSF3 promotes SRSF5 overexpression in oral squamous cell carcinoma cells by impairing the autoregulation mechanism of SRSF5. SRSF5 overexpression transforms immortal rodent fibroblasts to form tumors, and its downregulation retards cell growth, cell cycle progression, and tumor growth. |
RNAi knockdown, overexpression, focus formation/tumor formation assays in nude mice, western blotting |
Biochimica et biophysica acta. Molecular cell research |
Medium |
29857020
|
| 2024 |
LINC01852 lncRNA promotes TRIM72-mediated ubiquitination and degradation of SRSF5, thereby inhibiting SRSF5-mediated alternative splicing of PKM and decreasing PKM2 production, which induces a metabolic switch from glycolysis to oxidative phosphorylation and reduces chemoresistance in colorectal cancer. |
RNA pulldown, RNA immunoprecipitation, in vitro and in vivo functional experiments, ubiquitination assays, cell culture and mouse models |
Molecular cancer |
Medium |
38263157
|
| 2022 |
CPEB2 binds to and increases SRSF5 mRNA stability in glioma microvascular endothelial cells; increased SRSF5 protein then promotes ETS1 exon inclusion (producing P51-ETS1), which transcriptionally promotes expression of tight junction proteins ZO-1, occludin, and claudin-5 to regulate blood-tumor barrier permeability. |
RNA immunoprecipitation, knockdown experiments in in vitro BTB/BBB models and in vivo glioblastoma xenograft mice, western blotting, reporter assays |
Communications biology |
Medium |
36064747
|
| 2013 |
During erythroid cell differentiation, SRSF5 protein is targeted for proteasome-mediated degradation via its C-terminal RS domain, while SRSF5 mRNA is simultaneously upregulated. The RNA recognition motifs (RRMs) of SRSF5 are sufficient to activate pre-mRNA splicing, but the RS domain is required for proteasomal targeting. Inhibition of CLK kinase family and mutation of AKT phosphorylation site Ser86 had no effect on SRSF5 stability, indicating these pathways are not involved in this proteolytic turnover. |
Proteasome chemical inhibition, stable transfection of SRSF5 cDNA constructs, domain deletion/mutation analysis, splicing reporter assays in erythroid cell differentiation system |
PloS one |
Medium |
23536862
|
| 2021 |
Srsf5 knockout mice (generated by CRISPR-Cas9) are perinatally lethal and exhibit noncompaction of ventricular myocardium with cardiac dysfunction. Mechanistically, Srsf5 promotes alternative splicing of Myom1 (myomesin-1) to switch between embryonic and adult isoforms; this switch cannot be completed in Srsf5-deficient hearts. |
CRISPR-Cas9 knockout mouse generation, echocardiography, electrocardiography, RNA splicing analysis |
iScience |
High |
34622152
|
| 2017 |
SRSF5 transcript and protein levels are induced by mild hypothermia (32°C), DNA damage, hypoxia, cycloheximide, and hypotonicity in mammalian cells, identifying it as a cold-inducible protein. SRSF5 facilitates production of p19 H-RAS (an alternative splicing isoform) and increases sensitivity to doxorubicin. Induction of SRSF5 (as well as CIRP and RBM3) depends on TRPV4 channel protein but appears independent of its ion channel activity. |
Temperature shift experiments, immunohistochemistry, western blotting, TRPV4 inhibition/knockdown, doxorubicin sensitivity assays |
Scientific reports |
Medium |
28536481
|
| 2022 |
SRSF5, via its RRM2 domain, directly binds influenza A virus M mRNA at conserved sites (positions 163, 709, and 712), interacts with U1 snRNP, and promotes M mRNA splicing to produce M2 protein, thereby facilitating viral replication. Mutations at the three binding sites attenuate virus replication and pathogenesis in vivo. SRSF5 conditional knockout in lung protects mice from lethal IAV challenge. |
RNA-protein binding assays, domain mutagenesis (RRM2), Co-IP with U1 snRNP, site-directed mutagenesis of binding sites in viral genome, conditional knockout mice, in vivo IAV challenge |
Advanced science |
High |
36257906
|
| 2021 |
SRSF5 regulates alternative splicing of DMTF1 pre-mRNA by modulating SF1 binding to the DMTF1 pre-mRNA; SRSF5 binding competes with or modulates SF1 association to influence exon inclusion/skipping. |
RIP assays, CLIP-seq, splicing reporter assays, mutagenesis of splicing regulatory elements (ESE/ESS), co-immunoprecipitation |
RNA biology |
Medium |
34291726
|
| 2023 |
SRSF5 promotes alternative splicing of NCOR2 pre-mRNA to suppress production of the BQ323636.1 splice variant (exon 11 exclusion isoform). SRPK1 phosphorylates SRSF5, and inhibition of SRPK1 by SRPKIN-1 reduces SRSF5 phosphorylation, enhancing SRSF5 interaction with exon 11 of NCOR2 and reducing BQ mRNA production, thereby reversing tamoxifen resistance in ER-positive breast cancer. |
SRSF5 knockdown and overexpression, Co-IP (SRPK1-SRSF5 interaction), in vitro and in vivo studies, tissue microarray, phosphorylation assays with SRPKIN-1 inhibitor |
Cancers |
Medium |
37190199
|
| 2023 |
SRSF5 knockdown induces apoptosis through activation of caspase-3 in APL (NB4) cells, establishing SRSF5 as a pro-survival factor in leukemia. |
siRNA knockdown of SRSF5 in NB4 cells, caspase-3 activation assay, cell viability assays |
Archives of biochemistry and biophysics |
Low |
37356608
|
| 1997 |
The human SFRS5/SRp40 gene produces two major transcripts (~1.8-kb short form and ~3.3-kb long form) by alternative splicing (intron 5 retention in the long form); the short form encodes the SR splicing factor and at most the long form encodes a truncated protein with one RNA-binding domain. The gene was localized to chromosome 14q24. |
cDNA cloning, northern blotting, FISH, somatic cell hybrid PCR, immunofluorescence |
Genomics / Gene |
Medium |
9244433 9434190
|
| 2025 |
SRSF5 localizes to both nuclear speckles and the shell of a subset of paraspeckles. SRSF5 binds purine-rich sequences at the 5' end of NEAT1_2, promoting its alignment to paraspeckle shells and enabling large paraspeckle cluster formation during stress. SRSF5 depletion impairs paraspeckle formation; prolonged depletion triggers a feedback loop involving intron retention and premature polyadenylation of TARDBP mRNA, reducing TDP-43 levels and causing NEAT1_2 isoform switching that restores paraspeckle clusters. |
Super-resolution microscopy, rapid (acute) depletion system, proximity proteomics, iCLIP, rocaglamide A treatment, immunofluorescence |
Nucleic acids research |
High |
40716777
|
| 2025 |
SRSF5 silencing in trophoblast cells (HTR8/SVneo) induces alternative splicing of MLX pre-mRNA, leading to ubiquitination and proteasomal degradation of MLX protein. Loss of MLX enhances NR2F2 transcriptional activity, which inhibits trophoblast cell apoptosis. |
RT-PCR for alternative splicing, RIP assays, Co-IP, in vivo ubiquitination assays, siRNA knockdown, CCK8/wound healing/transwell/TUNEL assays |
FASEB journal |
Medium |
40586738
|
| 2026 |
The tRNA-derived small RNA CHAtRF directly interacts with SRSF5 and blocks SRSF5 from binding Psmg4 pre-mRNA, thereby promoting exon 2 skipping of Psmg4 and reducing full-length Psmg4 isoform expression, which drives pathological cardiac hypertrophy. |
RNA-protein binding assays (CHAtRF-SRSF5 interaction), SRSF5-Psmg4 pre-mRNA binding assays, splicing analysis, in vivo cardiac hypertrophy models, hiPSC-CMs |
Research (Washington, D.C.) |
Medium |
41907183
|