ArticleNucleic acids research2023
Alternative splicing of BCL-x is controlled by RBM25 binding to a G-quadruplex in BCL-x pre-mRNA.
Article in Nucleic acids research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 24 citations in OpenAlex.
- A machine learning model for periodontitis based on integrative gene expression analysis: validation in an independent patient cohort.Journal of periodontal & implant science · 2026Article
- RBM5 Acts as a Tumor Suppressor in Breast Cancer Through Binding to G-quadruplexes in the BAP1 Gene Promoter to Activate Its Expression.Molecules (Basel, Switzerland) · 2026Article
- RNF149/RBM25/MYC/PD-L1 axis promotes CD8Cellular oncology (Dordrecht, Netherlands) · 2026Article
- Arginine Methylation in Alternative Splicing: Implications for Cancer Therapy.Journal of cellular physiology · 2026Review
- Anti-apoptotic BCL-2 family proteins: from regulatory networks to therapeutic targeting.Oncogenesis · 2026Review
- RNA splicing in cancer cell death regulation: shedding light on the molecular mechanisms and potential clinical applications.Cell death & disease · 2026Review
- U2AF2-regulated alternative splicing of UPP1 promotes NSCLC progression by enhancing glycolysis.Cell communication and signaling : CCS · 2026Article
- Targeting the PBX1-BCL2L1 axis as a therapeutic strategy in colorectal cancer.Cell death discovery · 2026Article
- Inherent Specificity and Variation Sensitivity as Quantitative Metrics for RBP Binding.bioRxiv : the preprint server for biology · 2026Article
- Article
- G-quadruplex stabilization via small molecules as a potential anti-cancer strategy.Cellular & molecular biology letters · 2026Review
- RNA G-quadruplexes in oncogene regulation and as emerging targets for cancer therapy.Cell communication and signaling : CCS · 2026Review
- RNA-binding motif proteins as context-dependent regulators of tumor-immune crosstalk, genome stability, and therapeutic vulnerabilities in cancer.Frontiers in immunology · 2026Review
- G-quadruplexes in the proximity 3'-UTR enhances alternative polyadenylation of Neogenin 1.iScience · 2025Article
- Alternative Splicing: Molecular Mechanisms, Biological Functions, Diseases, and Potential Therapeutic Targets.MedComm · 2025Review
- The Epstein-Barr virus EBNA1 protein binds to G-quadruplexes in its own mRNA hence controlling its expression and immune evasion of the virus.Nucleic acids research · 2025Article
- Host factor RBM25 promotes HBV replication through Yin Yang 1-mediated cccDNA transcription.Virologica Sinica · 2025Article
- Alternative Splicing in Tumorigenesis and Cancer Therapy.Biomolecules · 2025Review
- Bioorthogonal Cyclopropenones for Investigating RNA Structure.ACS chemical biology · 2024Article
- RBM25 depletion suppresses the growth of colon cancer cells through regulating alternative splicing of MNK2.Science China. Life sciences · 2024Article
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BCL-x is a master regulator of apoptosis whose pre-mRNA is alternatively spliced into either a long (canonical) anti-apoptotic Bcl-xL isoform, or a short (alternative) pro-apoptotic Bcl-xS isoform. The balance between these two antagonistic isoforms is tightly regulated and overexpression of Bcl-xL has been linked to resistance to chemotherapy in several cancers, whereas overexpression of Bcl-xS is associated to some forms of diabetes and cardiac disorders. The splicing factor RBM25 controls alternative splicing of BCL-x: its overexpression favours the production of Bcl-xS, whereas its downregulation has the opposite effect. Here we show that RBM25 directly and specifically binds to GQ-2, an RNA G-quadruplex (rG4) of BCL-x pre-mRNA that forms at the vicinity of the alternative 5' splice site leading to the alternative Bcl-xS isoform. This RBM25/rG4 interaction is crucial for the production of Bcl-xS and depends on the RE (arginine-glutamate-rich) motif of RBM25, thus defining a new type of rG4-interacting domain. PhenDC3, a benchmark G4 ligand, enhances the binding of RBM25 to the GQ-2 rG4 of BCL-x pre-mRNA, thereby promoting the alternative pro-apoptotic Bcl-xS isoform and triggering apoptosis. Furthermore, the screening of a combinatorial library of 90 putative G4 ligands led to the identification of two original compounds, PhenDH8 and PhenDH9, superior to PhenDC3 in promoting the Bcl-xS isoform and apoptosis. Thus, favouring the interaction between RBM25 and the GQ-2 rG4 of BCL-x pre-mRNA represents a relevant intervention point to re-sensitize cancer cells to chemotherapy.
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