GSE184404
Mex3a RIP-seq
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 in pro-neural factors needed for neuronal fate. Although little is known about how stemness is molecularly balanced with the acquisition of the cell competence for neuronal differentiation along the lineage, regulated translation of existing transcripts is 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 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 the 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 acts via a number of downstream targets to function as a pivotal regulator of adult mammalian neurogenesis. Overall design: In order to identify MEX3A target RNAs, endogenous MEX3A was immunoprecipitated in FLAG-tagged NSC cultures (Mex3aFLAG/FLAG). Wild-type cultures from the same background that did not express the knock-in FLAG sequence were used as controls for nonspecific binding. 2-3 biological replicates for both the FLAG-tagged and the wild-type cultures were used and the IP was performed both with crosslinked and non-crosslinked samples.