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

Mostra el registre complet Registre parcial de l'ítem

  • dc.contributor.author González Iglesias, Ainara
  • dc.contributor.author Arcas Mantas, Aida
  • dc.contributor.author Domingo Muelas, Ana
  • dc.contributor.author Mancini, Estefanía
  • dc.contributor.author Galcerán, Joan
  • dc.contributor.author Valcárcel, J. (Juan)
  • dc.contributor.author Fariñas, Isabel
  • dc.contributor.author Nieto, M. Ángela
  • dc.date.accessioned 2024-08-01T11:55:21Z
  • dc.date.available 2024-08-01T11:55:21Z
  • dc.date.issued 2024
  • dc.description.abstract 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 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.
  • dc.description.sponsorship This work was supported by grants to M.A.N. from the Spanish Ministry of Science and Innovation (MCI PID2021-125682NB-I00), Instituto de Salud Carlos III (CIBERER/19/3.1), and Generalitat Valenciana (GVA) (ISIC 2012/010 plus Prometeo Programme 2017/150 and 2021/045). Work in I.F.’s lab was supported by MICIU grants PID2020-117937GB-I00, RED2018- 102723-T, CB06/05/0086 (CIBERNED), and RD16/0011/0017 (RETIC Tercel) plus Prometeo 2017/030. Work in J.V.’s lab was supported by MICIU PID2020-114630GB-I00 and ERC-AdG-LS2-670146I and the Generalitat de Catalunya through the CERCA programme. M.A.N. and J.V. also acknowledge financial support from the Spanish State Research Agency, through the ‘Severo Ochoa Programme’ for Centres of Excellence in R&D, Grants CEX2021-001165-S and CEX2020-001049-S, respectively. A.G.-I. was holder of a FPU predoctoral contract from the Spanish Ministry of Education, Culture and Sports.
  • dc.format.mimetype application/pdf
  • dc.identifier.citation González-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-z
  • dc.identifier.doi http://dx.doi.org/10.1038/s41467-024-47092-z
  • dc.identifier.issn 2041-1723
  • dc.identifier.uri http://hdl.handle.net/10230/60879
  • dc.language.iso eng
  • dc.publisher Nature Research
  • dc.relation.ispartof Nat Commun. 2024 Apr 2;15(1):2837
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/670146
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/3PE/PID2021-125682NB-I00
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PID2020-117937GB-I00
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/RED2018- 102723-T
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PID2020-114630GB-I00
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/3PE/CEX2021-001165-S
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/CEX2020-001049-S
  • dc.rights © 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/.
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by/4.0/
  • dc.subject.keyword RNA transport
  • dc.subject.keyword Stem cells in the nervous system
  • dc.title Intron detention tightly regulates the stemness/differentiation switch in the adult neurogenic niche
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

Col·leccions

Articles (Center for Genomic Regulation (CRG))
Articles (Departament de Medicina i Ciències de la Vida)
Documents OpenAIRE (Open Access Infrastructure for Research in Europe)