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Post-transcriptional control of a stemness signature by RNA-binding 8 protein MEX3A regulates adult neurogenesis

ABSTRACT: Neural stem cells (NSCs) in the adult mammalian subependymal zone maintain a glial identity and the developmental potential to generate neurons during the lifetime. Production of neurons from these NSCs is not direct but follows an orderly pattern of cell progression which allows the gradual increase along the neurogenic lineage in the expression of pro-neural factors needed for neuronal specification. In this context, tightly regulated translation of existing transcriptional programs represents a potential mechanism to avoid the critical challenge posed by genes that encode proteins with conflicting functions, i.e. self-renew or differentiate. Here, we identify RNA-binding protein MEX3A as a post-transcriptional regulator of a set of stemness-associated transcripts at critical transitions in the subependymal neurogenic lineage. MEX3A binding to a set of quiescence-related RNAs in activated NSCs is needed for their return to quiescence, playing a role in the long-term maintenance of the NSC pool. Furthermore, it is required for the repression of the same program at the onset of neuronal differentiation. Our data indicate that MEX3A is a pivotal regulator of adult mammalian neurogenesis acting as a translational remodeller.

INSTRUMENT(S): TripleTOF 5600

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain

SUBMITTER: Luz Valero

LAB HEAD: Isabel Fariñas

PROVIDER: PXD038983 | Pride | 2023-01-08

REPOSITORIES: Pride

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