González Iglesias, AinaraArcas Mantas, AidaDomingo Muelas, AnaMancini, EstefaníaGalcerán, JoanValcárcel, J. (Juan)Fariñas, IsabelNieto, M. Ángela2024-08-012024-08-012024González-Iglesias A, Arcas A, Domingo-Muelas A, Mancini E, Galcerán J, Valcárcel J, et al. Intron detention tightly regulates the stemness/differentiation switch in the adult neurogenic niche. Nat Commun. 2024 Apr 2;15(1):2837. DOI: 10.1038/s41467-024-47092-z2041-1723http://hdl.handle.net/10230/60879The adult mammalian brain retains some capacity to replenish neurons and glia, holding promise for brain regeneration. Thus, understanding the mechanisms controlling adult neural stem cell (NSC) differentiation is crucial. Paradoxically, adult NSCs in the subependymal zone transcribe genes associated with both multipotency maintenance and neural differentiation, but the mechanism that prevents conflicts in fate decisions due to these opposing transcriptional programmes is unknown. Here we describe intron detention as such control mechanism. In NSCs, while multiple mRNAs from stemness genes are spliced and exported to the cytoplasm, transcripts from differentiation genes remain unspliced and detained in the nucleus, and the opposite is true under neural differentiation conditions. We also show that m6A methylation is the mechanism that releases intron detention and triggers nuclear export, enabling rapid and synchronized responses. m6A RNA methylation operates as an on/off switch for transcripts with antagonistic functions, tightly controlling the timing of NSCs commitment to differentiation.application/pdfeng© The Author(s) 2024, corrected publication 2024. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.info:eu-repo/semantics/articlehttp://dx.doi.org/10.1038/s41467-024-47092-zRNA transportStem cells in the nervous systeminfo:eu-repo/semantics/openAccess