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

Ana Domingo-Muelas, Pere Duart-Abadia, Jose Manuel Morante-Redolat, Antonio Jordán-Pla, Germán Belenguer, Jaime Fabra-Beser, Lucía Paniagua-Herranz, Ana Pérez-Villalba, Adrián Álvarez-Varela, Francisco M. Barriga, Cristina Gil-Sanz, Felipe Ortega, Eduard Batlle () and Isabel Fariñas ()
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Ana Domingo-Muelas: Universidad de Valencia
Pere Duart-Abadia: Universidad de Valencia
Jose Manuel Morante-Redolat: Universidad de Valencia
Antonio Jordán-Pla: Universidad de Valencia
Germán Belenguer: Universidad de Valencia
Jaime Fabra-Beser: Universidad de Valencia
Lucía Paniagua-Herranz: Universidad Complutense de Madrid (UCM)
Ana Pérez-Villalba: Universidad de Valencia
Adrián Álvarez-Varela: Institute for Research in Biomedicine (IRB Barcelona)
Francisco M. Barriga: Institute for Research in Biomedicine (IRB Barcelona)
Cristina Gil-Sanz: Universidad de Valencia
Felipe Ortega: Universidad Complutense de Madrid (UCM)
Eduard Batlle: Institute for Research in Biomedicine (IRB Barcelona)
Isabel Fariñas: Universidad de Valencia

Nature Communications, 2023, vol. 14, issue 1, 1-17

Abstract: Abstract Neural stem cells (NSCs) in the adult murine subependymal zone balance their self-renewal capacity and glial identity with the potential to generate neurons during the lifetime. Adult NSCs exhibit lineage priming via pro-neurogenic fate determinants. However, the protein levels of the neural fate determinants are not sufficient to drive direct differentiation of adult NSCs, which raises the question of how cells along the neurogenic lineage avoid different conflicting fate choices, such as self-renewal and differentiation. 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 regulates a quiescence-related RNA signature in activated NSCs that 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 murine neurogenesis acting as a translational remodeller.

Date: 2023
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DOI: 10.1038/s41467-023-36054-6

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