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

Author

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  • Ainara González-Iglesias

    (Instituto de Neurociencias (CSIC-UMH))

  • Aida Arcas

    (Instituto de Neurociencias (CSIC-UMH)
    University of Navarra)

  • Ana Domingo-Muelas

    (Universidad de Valencia
    Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED)
    Carlos Simon Foundation
    University of Pennsylvania)

  • Estefania Mancini

    (The Barcelona Institute of Science and Technology)

  • Joan Galcerán

    (Instituto de Neurociencias (CSIC-UMH)
    Centro de Investigación Biomédica en Red sobre Enfermedades Raras (CIBERER))

  • Juan Valcárcel

    (The Barcelona Institute of Science and Technology
    Universitat Pompeu Fabra (UPF)
    Institució Catalana de Recerca i Estudis Avançats (ICREA))

  • Isabel Fariñas

    (Universidad de Valencia
    Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED))

  • M. Angela Nieto

    (Instituto de Neurociencias (CSIC-UMH)
    Centro de Investigación Biomédica en Red sobre Enfermedades Raras (CIBERER))

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.

Suggested Citation

  • Ainara González-Iglesias & Aida Arcas & Ana Domingo-Muelas & Estefania Mancini & Joan Galcerán & Juan Valcárcel & Isabel Fariñas & M. Angela Nieto, 2024. "Intron detention tightly regulates the stemness/differentiation switch in the adult neurogenic niche," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-47092-z
    DOI: 10.1038/s41467-024-47092-z
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    References listed on IDEAS

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