Systematic exploration of dynamic splicing networks reveals conserved multistage regulators of neurogenesis.
RNA-binding proteins
alternative splicing
gene regulation
high-throughput screening
neurogenesis
single-cell profiling
Journal
Molecular cell
ISSN: 1097-4164
Titre abrégé: Mol Cell
Pays: United States
ID NLM: 9802571
Informations de publication
Date de publication:
18 08 2022
18 08 2022
Historique:
received:
10
11
2021
revised:
16
04
2022
accepted:
29
06
2022
pubmed:
2
8
2022
medline:
24
8
2022
entrez:
1
8
2022
Statut:
ppublish
Résumé
Alternative splicing (AS) is a critical regulatory layer; yet, factors controlling functionally coordinated splicing programs during developmental transitions are poorly understood. Here, we employ a screening strategy to identify factors controlling dynamic splicing events important for mammalian neurogenesis. Among previously unknown regulators, Rbm38 acts widely to negatively control neural AS, in part through interactions mediated by the established repressor of splicing, Ptbp1. Puf60, a ubiquitous factor, is surprisingly found to promote neural splicing patterns. This activity requires a conserved, neural-differential exon that remodels Puf60 co-factor interactions. Ablation of this exon rewires distinct AS networks in embryonic stem cells and at different stages of mouse neurogenesis. Single-cell transcriptome analyses further reveal distinct roles for Rbm38 and Puf60 isoforms in establishing neuronal identity. Our results describe important roles for previously unknown regulators of neurogenesis and establish how an alternative exon in a widely expressed splicing factor orchestrates temporal control over cell differentiation.
Identifiants
pubmed: 35914530
pii: S1097-2765(22)00654-2
doi: 10.1016/j.molcel.2022.06.036
pmc: PMC10686216
mid: NIHMS1941304
pii:
doi:
Substances chimiques
RNA-Binding Proteins
0
Rbm38 protein, mouse
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2982-2999.e14Subventions
Organisme : Intramural NIH HHS
ID : ZIA BC012019
Pays : United States
Informations de copyright
Copyright © 2022. Published by Elsevier Inc.
Déclaration de conflit d'intérêts
Declaration of interests B.J.B. and A.-C.G. are members of the Molecular Cell advisory board. The remaining authors declare no competing interests.
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