| 2008 |
RBM25 functions as a splicing factor that promotes pro-apoptotic Bcl-x(S) 5' splice site selection in a dose-dependent manner. RBM25 directly binds a CGGGCA exonic element in BCL-x pre-mRNA exon 2; mutation of this element abolishes Bcl-x(S) isoform production. RBM25 promotes recruitment of U1 snRNP to the weak Bcl-x(S) 5' splice site, and specifically associates with the U1 snRNP-associated factor hLuc7A. |
RNA binding assays, splice site reporter mutagenesis, RNAi depletion, Co-IP with hLuc7A, U1 snRNP recruitment assay |
Molecular and cellular biology |
High |
18663000
|
| 2011 |
RBM25 and LUC7L3 are upregulated in human heart failure and together mediate aberrant truncation of SCN5A (cardiac sodium channel) mRNA. Overexpression of either factor in Jurkat cells and human embryonic stem cell-derived cardiomyocytes increases truncated SCN5A mRNA while decreasing full-length transcript, reducing Na+ channel current by ~91%. |
Gene array profiling, overexpression in cell lines and ESC-derived cardiomyocytes, RT-PCR for splice variants, patch-clamp electrophysiology |
Circulation |
High |
21859973
|
| 2012 |
In heart failure, angiotensin II and hypoxia signals increase RBM25 expression, leading to increased binding of RBM25 to SCN5A mRNA, increased SCN5A splice variant production, decreased full-length SCN5A mRNA and protein, and decreased Na+ current, linking upstream HF signals to RBM25-mediated splicing dysregulation. |
RIP (RNA immunoprecipitation), RT-PCR, Western blot, patch clamp, cell treatment with angiotensin II and hypoxia |
Trends in cardiovascular medicine |
Medium |
22939879
|
| 2013 |
Crystal structure of the human RBM25 PWI domain and its flanking basic region was determined. The PWI domain comprises a conserved four-helix bundle; the flanking basic region forms two α-helices that associate with helix H4 of the PWI domain, creating an enlarged nucleic-acid-binding platform. Structure-guided mutagenesis identified a positively charged nucleic-acid-binding surface distinct from that in SRm160. The PWI domain was shown to be required in vivo for RBM25-mediated promotion of pro-apoptotic Bcl-xS isoform expression. |
X-ray crystallography, structure-guided mutagenesis, functional splicing assay in cells |
The Biochemical journal |
High |
23190262
|
| 2017 |
RBM25 is an essential global splicing factor required for viability of multiple human cell lines. Transcriptome-wide analysis showed RBM25 regulates a large fraction of alternatively spliced exons genome-wide, predominantly promoting exon inclusion. Proteomic analysis identified RBM25 interactions with components of the early spliceosome and alternative splicing regulators. RBM25 is mono-methylated at lysine 77 (K77me1), and the unmethylated K77-containing region binds with high affinity to SRSF2 (a key exon definition factor), whereas K77me1 abrogates this interaction, revealing a methylation-dependent regulatory mechanism. |
shRNA knockdown cell viability, RNA-seq (transcriptome-wide splicing analysis), AP-MS proteomics, quantitative mass spectrometry for K77me1, in vitro binding assays with SRSF2, mutagenesis |
The Journal of biological chemistry |
High |
28655759
|
| 2018 |
p53 directly activates the RBM25 gene transcriptionally, and RBM25 protein binds directly to circAMOTL1L (a circular RNA derived from the AMOTL1 locus) and induces its biogenesis, thereby linking the p53/RBM25 axis to circRNA production and EMT regulation in prostate cancer. |
ChIP for p53 binding at RBM25 promoter, RBM25 knockdown/overexpression, RNA pull-down for RBM25-circAMOTL1L interaction, circRNA biogenesis assays |
Oncogene |
Medium |
30531834
|
| 2019 |
In acute myeloid leukemia, RBM25 acts as a tumor suppressor by controlling splicing of BCL-X (promoting pro-apoptotic Bcl-xS) and BIN1 (a MYC inhibitor). RBM25 knockdown promotes proliferation and decreases apoptosis in multiple human leukemic cell lines, and low RBM25 levels are associated with high MYC activity. |
In vivo shRNA screen in mouse AML model, shRNA knockdown in human leukemic cell lines, RNA-seq splicing analysis, proliferation and apoptosis assays |
Nature communications |
High |
30635567
|
| 2023 |
RBM25 directly and specifically binds GQ-2, an RNA G-quadruplex (rG4) located near the alternative Bcl-xS 5' splice site in BCL-x pre-mRNA. This interaction depends on the RE (arginine-glutamate-rich) motif of RBM25, defining a new rG4-interacting domain. The RBM25/rG4 interaction is required for Bcl-xS production, and G4 ligands that stabilize the rG4 enhance RBM25 binding and promote Bcl-xS isoform expression and apoptosis. |
In vitro binding assays (EMSA, pull-down), mutagenesis of RBM25 RE motif, G4-ligand treatment, splicing reporter assays, apoptosis assays |
Nucleic acids research |
High |
37811881
|
| 2023 |
RBM25 deficiency in macrophages leads to increased proinflammatory gene expression coupled with histone acetylation changes (H3K9ac, H3K27ac) and HIF-1α activity. Mechanistically, RBM25 directly binds ACLY pre-mRNA and mediates skipping of exon 14, generating two distinct isoforms: Acly Long (Acly L) and Acly Short (Acly S). In proinflammatory macrophages, Acly L undergoes protein lactylation on K918/K995 whereas Acly S does not, affecting metabolic substrate affinity and acetyl-CoA production. Macrophage-specific RBM25 deletion causes spontaneous arthritis and multi-organ inflammation in mice, reversible by Acly inhibition. |
Conditional knockout mice, multiomics (RNA-seq, ATAC-seq, ChIP-seq), RIP for RBM25-ACLY pre-mRNA binding, splicing reporter assays, metabolic assays, lactylation proteomics |
Cellular & molecular immunology |
High |
39251781
|
| 2023 |
METTL3-mediated m6A methylation stabilizes RBM25 mRNA; metformin reduces METTL3 activity, decreasing m6A on RBM25 mRNA and reducing RBM25 mRNA stability and expression in multiple myeloma cells, contributing to anti-proliferative effects. |
MeRIP (m6A RNA immunoprecipitation), METTL3 knockdown/overexpression, mRNA stability assays, rescue experiments, xenograft mouse model |
Cell cycle |
Medium |
36762777
|
| 2023 |
RBM25 binds to and regulates alternative splicing of Slc38a9, Csf1, and Coro6 in H9c2 cardiomyoblasts, as identified by iRIP-seq; RBM25 overexpression upregulates genes involved in inflammatory response and mediates alternative splicing of apoptosis- and inflammation-related genes. |
RNA-seq, iRIP-seq, RT-qPCR validation, overexpression in H9c2 cells |
PeerJ |
Medium |
37953772
|
| 2023 |
RBM25 is upregulated in ischemic heart failure and hypoxia-injured cardiomyocytes, localizes to the nucleus, and promotes cardiomyocyte apoptosis through upregulation of ER stress and the CHOP signaling pathway. Knockdown of RBM25 ameliorates apoptosis and improves cardiac function in a rat ischemic HF model. |
In vivo rat ischemic HF model, OGD in vitro model, Western blot, immunofluorescence, ER-tracker staining, echocardiography, RBM25 knockdown/overexpression |
Cell stress & chaperones |
Medium |
37736860
|
| 2024 |
dCasRx fused to RBM25 (dCasRx-RBM25) acts as a potent, specific activator of endogenous alternative exon splicing when targeted by guide RNAs, efficiently activating ~90% of targeted endogenous alternative exons with high on-target specificity and enabling multiplexed combinatorial exon activation/repression. |
CRISPR-dCasRx fusion screen (>300 constructs), splicing reporter assays, endogenous gene targeting, gRNA array combinatorial experiments, RNA-seq specificity analysis |
Molecular cell |
High |
38917795
|
| 2024 |
RBM25 regulates alternative splicing of MNK2 in colon cancer by binding a poly-G-rich region in exon 14a, inhibiting selection of the proximal 3' splice site and promoting production of the oncogenic short isoform MNK2b over the tumor-suppressive MNK2a. RBM25 depletion shifts the balance toward MNK2a and suppresses colon cancer cell growth in vitro and in vivo. |
Transcriptome-wide RNA-seq, RIP for RBM25-MNK2 pre-mRNA binding, ASO blocking of splice site, MNK2b re-expression rescue, xenograft mouse model |
Science China. Life sciences |
High |
39110401
|
| 2025 |
RBM25 promotes HBV replication by binding to cccDNA through its RE/RD and PWI domains, upregulating Yin Yang 1 (YY1) expression, which enhances histone acetylation on cccDNA, thereby promoting HBV transcription. HBV core protein accumulation induces nuclear translocation of RBM25 and promotes its expression, while RBM25 overexpression promotes core protein degradation, revealing a reciprocal regulatory loop. |
RBM25 knockdown/overexpression in HBV-replicating cell models and hydrodynamic injection mouse model, ChIP for cccDNA binding, domain mutagenesis (RE/RD and PWI), YY1 expression analysis, histone acetylation assays |
Virologica Sinica |
Medium |
40412480
|
| 2025 |
RBM25 induces exon 16 skipping in MAP4K4 pre-mRNA in a rat post-infarction heart failure model, generating a truncated MAP4K4 isoform that activates the p38 MAPK signaling pathway. RBM25 overexpression exacerbates myocardial injury and apoptosis, while knockdown is protective; p38 MAPK inhibition attenuates RBM25-mediated myocardial injury. |
LAD ligation rat HF model, lentiviral RBM25 OE/shRNA, qPCR for MAP4K4 splice variants, echocardiography, TUNEL, Western blot for MAPK pathway components, pharmacological p38 inhibition/activation rescue |
FASEB bioAdvances |
Medium |
41409803
|
| 2025 |
In pulmonary artery smooth muscle cells, lncRNA-536 acts as a decoy for RBM25, sequestering it and preventing RBM25 from binding SFPQ (a transcriptional regulator). When RBM25 is free (lnc-536 low), it sequesters SFPQ, reducing SFPQ-HOXB13 mRNA interactions and leading to decreased HOXB13 expression and smooth muscle hyperproliferation. RBM25 knockdown reverses SFPQ-HOXB13 interactions and attenuates PASMC proliferation. |
RNA pull-down for lnc-536/RBM25 interaction, RNA-IP with SFPQ antibody showing direct RBM25-SFPQ interaction, knockdown/overexpression of lnc-536 and RBM25, in vivo GapmeR injection in pulmonary hypertension rat models |
Arteriosclerosis, thrombosis, and vascular biology |
Medium |
40567228
|
| 2025 |
Rbm25 occupies promoters of pluripotency genes and DNA methylation-related genes in embryonic stem cells and directly regulates their transcription, thereby governing ESC identity and epigenetic state. Loss of Rbm25 impairs ESC self-renewal and differentiation while promoting transition toward totipotent-like 2-cell-like cells (2CLCs). |
Rbm25 conditional knockout/depletion in ESCs, ChIP-seq for Rbm25 promoter occupancy, RNA-seq, 2CLC reporter assays, differentiation assays |
Stem cell reports |
Medium |
41455468
|
| 2026 |
Conditional homozygous knockout of Rbm25 in mice causes collapse of hematopoiesis affecting multiple lineages including long-term hematopoietic stem cells and embryonic stem cells, demonstrating that RBM25 is essential for normal hematopoietic maintenance. Mono-allelic deletion is haplosufficient and does not impair HSC self-renewal or differentiation under steady-state or proliferative stress. |
Conditional knock-out mouse model, bone marrow transplantation, flow cytometry of hematopoietic lineages, proliferative stress assays |
Experimental cell research |
High |
41819468
|
| 2023 |
Rbm25 knockdown accelerates expansion of Tet2-knockout hematopoietic stem cells in vitro and in vivo, demonstrating that variability in Rbm25 expression downstream of Tet2 loss drives heterogeneous preleukemic clonal expansion. |
Genetic barcoding of HSCs in inducible Tet2 KO mouse model, shRNA knockdown of Rbm25, in vitro and in vivo HSC expansion assays |
Blood |
Medium |
36947858
|
| 2025 |
RBM25 exhibits low inherent RNA-binding specificity compared to high-specificity RBPs such as HNRNPC. RNA binding domain swap CLIP experiments between RBM25 and HNRNPC demonstrated that sequence specificity can be transferred between protein contexts, and low-specificity RBPs like RBM25 can functionally enhance the specificity of high-specificity RBPs by occupying non-target sites. |
High-throughput sequencing of CLIP datasets, domain swap CLIP experiments, quantitative specificity metrics (inherent specificity and mutational sensitivity) |
bioRxivpreprint |
Low |
bio_10.1101_2025.03.28.646018
|