ArticleMolecular biology of the cell2016
RBM4 promotes neuronal differentiation and neurite outgrowth by modulating Numb isoform expression.
Article in Molecular biology of the cell, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 34 citations in OpenAlex.
- Integrative transcriptomic analysis reveals alternative splicing programs in sepsis-induced myocardial injury across dual mouse models.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- In-Cell Proteomics Enables High-Resolution Spatial and Temporal Mapping of Early Xenopus tropicalis Embryos.Molecular & cellular proteomics : MCP · 2026Article
- RBM4-mediated intron excision of Hsf1 induces BDNF for cerebellar foliation.Communications biology · 2024Article
- Bmlark is essential for embryonic development.BMC genomics · 2024Article
- Regulation of DNA damage response by RNA/DNA-binding proteins: Implications for neurological disorders and aging.Ageing research reviews · 2024Review
- Post-transcriptional regulation of the transcriptional apparatus in neuronal development.Frontiers in molecular neuroscience · 2024Review
- SPTAN1/NUMB axis senses cell density to restrain cell growth and oncogenesis through Hippo signaling.The Journal of clinical investigation · 2023Article
- Activation of TrkB signaling mitigates cerebellar anomalies caused by Rbm4-Bdnf deficiency.Communications biology · 2023Article
- Hypergravity enhances RBM4 expression in human bone marrow-derived mesenchymal stem cells and accelerates their differentiation into neurons.Regenerative therapy · 2023Article
- The X-linked splicing regulator MBNL3 has been co-opted to restrict placental growth in eutherians.PLoS biology · 2022Article
- RBM22, a Key Player of Pre-mRNA Splicing and Gene Expression Regulation, Is Altered in Cancer.Cancers · 2022Review
- Modulation of alternative splicing during early infection of human primary B lymphocytes with Epstein-Barr virus (EBV): a novel function for the viral EBNA-LP protein.Nucleic acids research · 2021Article
- The role of NUMB/NUMB isoforms in cancer stem cells.BMB reports · 2021Review
- A splicing factor switch controls hematopoietic lineage specification of pluripotent stem cells.EMBO reports · 2021Article
- tappAS: a comprehensive computational framework for the analysis of the functional impact of differential splicing.Genome biology · 2020Article
- DPYSL2 is a novel regulator for neural stem cell differentiation in rats: revealed by Panax notoginseng saponin administration.Stem cell research & therapy · 2020Article
- RBM4 modulates the proliferation and expression of inflammatory factors via the alternative splicing of regulatory factors in HeLa cells.Molecular genetics and genomics : MGG · 2020Article
- The Role of Dynamic miRISC During Neuronal Development.Frontiers in molecular biosciences · 2020Review
- Inadequate DNA Damage Repair Promotes Mammary Transdifferentiation, Leading to BRCA1 Breast Cancer.Cell · 2019Article
- RBM4 Modulates Radial Migration via Alternative Splicing of Dab1 during Cortex Development.Molecular and cellular biology · 2018Article
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
RBM4 participates in cell differentiation by regulating tissue-specific alternative pre-mRNA splicing. RBM4 also has been implicated in neurogenesis in the mouse embryonic brain. Using mouse embryonal carcinoma P19 cells as a neural differentiation model, we observed a temporal correlation between RBM4 expression and a change in splicing isoforms of Numb, a cell-fate determination gene. Knockdown of RBM4 affected the inclusion/exclusion of exons 3 and 9 of Numb in P19 cells. RBM4-deficient embryonic mouse brain also exhibited aberrant splicing of Numb pre-mRNA. Using a splicing reporter minigene assay, we demonstrated that RBM4 promoted exon 3 inclusion and exon 9 exclusion. Moreover, we found that RBM4 depletion reduced the expression of the proneural gene Mash1, and such reduction was reversed by an RBM4-induced Numb isoform containing exon 3 but lacking exon 9. Accordingly, induction of ectopic RBM4 expression in neuronal progenitor cells increased Mash1 expression and promoted cell differentiation. Finally, we found that RBM4 was also essential for neurite outgrowth from cortical neurons in vitro. Neurite outgrowth defects of RBM4-depleted neurons were rescued by RBM4-induced exon 9-lacking Numb isoforms. Therefore our findings indicate that RBM4 modulates exon selection of Numb to generate isoforms that promote neuronal cell differentiation and neurite outgrowth.
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