Intron detention tightly regulates the stemness/differentiation switch in the adult neurogenic niche.

Autor: González-Iglesias A; Instituto de Neurociencias (CSIC-UMH), Sant Joan d'Alacant, 03550, Spain., Arcas A; Instituto de Neurociencias (CSIC-UMH), Sant Joan d'Alacant, 03550, Spain.; Department of Gene Therapy and Regulation of Gene Expression, Center for Applied Medical Research, University of Navarra, Pamplona, 31008, Spain., Domingo-Muelas A; Departamento de Biología Celular, Biología Funcional y Antropología Física and Instituto de Biotecnología y Biomedicina, Universidad de Valencia, Burjassot, 46100, Spain.; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), 28029, Madrid, Spain.; Carlos Simon Foundation, 46980, Paterna, Valencia, Spain.; Department of Cell and Developmental Biology, Institute for Regenerative Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.; Igenomix Foundation, 46980, Paterna, Valencia, Spain., Mancini E; Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Barcelona, 08003, Spain., Galcerán J; Instituto de Neurociencias (CSIC-UMH), Sant Joan d'Alacant, 03550, Spain.; Centro de Investigación Biomédica en Red sobre Enfermedades Raras (CIBERER), 28029, Madrid, Spain., Valcárcel J; Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Barcelona, 08003, Spain.; Universitat Pompeu Fabra (UPF), 08003, Barcelona, Spain.; Institució Catalana de Recerca i Estudis Avançats (ICREA), 08010, Barcelona, Spain., Fariñas I; Departamento de Biología Celular, Biología Funcional y Antropología Física and Instituto de Biotecnología y Biomedicina, Universidad de Valencia, Burjassot, 46100, Spain.; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), 28029, Madrid, Spain., Nieto MA; Instituto de Neurociencias (CSIC-UMH), Sant Joan d'Alacant, 03550, Spain. anieto@umh.es.; Centro de Investigación Biomédica en Red sobre Enfermedades Raras (CIBERER), 28029, Madrid, Spain. anieto@umh.es.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Apr 02; Vol. 15 (1), pp. 2837. Date of Electronic Publication: 2024 Apr 02.
DOI: 10.1038/s41467-024-47092-z
Abstrakt: The 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 m 6 A methylation is the mechanism that releases intron detention and triggers nuclear export, enabling rapid and synchronized responses. m 6 A RNA methylation operates as an on/off switch for transcripts with antagonistic functions, tightly controlling the timing of NSCs commitment to differentiation.
(© 2024. The Author(s).)
Databáze: MEDLINE
Externí odkaz: