ArticleGenes & development2013
Regulation of constitutive and alternative splicing by PRMT5 reveals a role for Mdm4 pre-mRNA in sensing defects in the spliceosomal machinery.
Article in Genes & development, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 196 papers.
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196 citing papers in PubMed, 314 citations in OpenAlex.
- PRMT5-mediated intron retention triggers innate and adaptive immunity against cancer.EMBO molecular medicine · 2026Article
- Review
- Stage-Specific Degradation of Cyclin D3 Orchestrates Myelopoiesis and Restrains Myeloproliferative Neoplasm Development.Cancer research · 2026Article
- Inhibition of PRMT5 sensitizes B-cell non-Hodgkin lymphoma cells to both intrinsic and extrinsic apoptotic cell death.Blood neoplasia · 2026Article
- MTAP Deficiency as a Metabolic Vulnerability in Cancer: Implications for Synthetic Lethal Therapy.Cancer science · 2026Review
- PRMT5 inhibition promotes cross-species spermatogonia expansion and suppresses differentiation.Cell regeneration (London, England) · 2026Article
- Arginine Methylation in Alternative Splicing: Implications for Cancer Therapy.Journal of cellular physiology · 2026Review
- PRMT5-Cacna1d axis maintains calcium homeostasis to regulate postnatal motor development in mice.Cellular and molecular life sciences : CMLS · 2026Article
- Pharmacological targeting of SF3a1-MDM4 splicing vulnerability in ovarian cancer with rifaximin and antisense oligonucleotide.Journal of translational medicine · 2026Article
- Protein arginine methyltransferases in cancer: mechanisms, functions, and therapeutic opportunities.Journal of biomedical science · 2026Review
- A synergistic interaction between PRMT5 and LSD1 inhibitors in AML.Science advances · 2026Article
- Protein Arginine Methyltransferases in γ-Globin Regulation and Sickle Cell Disease: Emerging Connections to Oxidative Stress.Antioxidants (Basel, Switzerland) · 2026Review
- Article
- PRMT5 inhibitors actively promote metastatic progression of lung adenocarcinoma.bioRxiv : the preprint server for biology · 2026Article
- Interferon-Driven Biomarkers and Synergistic Therapy for PRMT5 Inhibition in Triple-Negative Breast Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The Role of Histone Methylation in Heart Failure: Epigenetic Mechanisms and Therapeutic Perspectives.Drug design, development and therapy · 2026Review
- Protein arginine methyltransferases in cardiovascular disease: mechanisms, therapeutic potential, and future directions.Frontiers in physiology · 2026Review
- Arginine methylation in cancer: mechanisms and therapeutic implications.Biomarker research · 2025Review
- Protein arginine methyltransferase 5 sustains Tip60-EP400 complex via SRSF1 in Merkel cell carcinoma.Life science alliance · 2025Article
- The role of ASXL1, SRSF2, and EZH2 mutations in chromatin dysregulation of myelodysplastic neoplasia and acute myeloid leukemia.Leukemia · 2025Review
136 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The tight control of gene expression at the level of both transcription and post-transcriptional RNA processing is essential for mammalian development. We here investigate the role of protein arginine methyltransferase 5 (PRMT5), a putative splicing regulator and transcriptional cofactor, in mammalian development. We demonstrate that selective deletion of PRMT5 in neural stem/progenitor cells (NPCs) leads to postnatal death in mice. At the molecular level, the absence of PRMT5 results in reduced methylation of Sm proteins, aberrant constitutive splicing, and the alternative splicing of specific mRNAs with weak 5' donor sites. Intriguingly, the products of these mRNAs are, among others, several proteins regulating cell cycle progression. We identify Mdm4 as one of these key mRNAs that senses the defects in the spliceosomal machinery and transduces the signal to activate the p53 response, providing a mechanistic explanation of the phenotype observed in vivo. Our data demonstrate that PRMT5 is a master regulator of splicing in mammals and uncover a new role for the Mdm4 pre-mRNA, which could be exploited for anti-cancer therapy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.