Intron detention tightly regulates the stemness/differentiation switch in the adult neurogenic niche
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...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-04-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-47092-z |
| _version_ | 1797219724792168448 |
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| author | Ainara González-Iglesias Aida Arcas Ana Domingo-Muelas Estefania Mancini Joan Galcerán Juan Valcárcel Isabel Fariñas M. Angela Nieto |
| author_facet | Ainara González-Iglesias Aida Arcas Ana Domingo-Muelas Estefania Mancini Joan Galcerán Juan Valcárcel Isabel Fariñas M. Angela Nieto |
| author_sort | Ainara González-Iglesias |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-24T12:38:12Z |
| format | Article |
| id | doaj.art-4116623c87df4b3fb1ecede9d29f1a58 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-04-24T12:38:12Z |
| publishDate | 2024-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-4116623c87df4b3fb1ecede9d29f1a582024-04-07T11:23:42ZengNature PortfolioNature Communications2041-17232024-04-0115111810.1038/s41467-024-47092-zIntron detention tightly regulates the stemness/differentiation switch in the adult neurogenic nicheAinara González-Iglesias0Aida Arcas1Ana Domingo-Muelas2Estefania Mancini3Joan Galcerán4Juan Valcárcel5Isabel Fariñas6M. Angela Nieto7Instituto de Neurociencias (CSIC-UMH)Instituto de Neurociencias (CSIC-UMH)Departamento de Biología Celular, Biología Funcional y Antropología Física and Instituto de Biotecnología y Biomedicina, Universidad de ValenciaCentre for Genomic Regulation (CRG), The Barcelona Institute of Science and TechnologyInstituto de Neurociencias (CSIC-UMH)Carlos Simon FoundationDepartamento de Biología Celular, Biología Funcional y Antropología Física and Instituto de Biotecnología y Biomedicina, Universidad de ValenciaInstituto de Neurociencias (CSIC-UMH)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.https://doi.org/10.1038/s41467-024-47092-z |
| spellingShingle | Ainara González-Iglesias Aida Arcas Ana Domingo-Muelas Estefania Mancini Joan Galcerán Juan Valcárcel Isabel Fariñas M. Angela Nieto Intron detention tightly regulates the stemness/differentiation switch in the adult neurogenic niche Nature Communications |
| title | Intron detention tightly regulates the stemness/differentiation switch in the adult neurogenic niche |
| title_full | Intron detention tightly regulates the stemness/differentiation switch in the adult neurogenic niche |
| title_fullStr | Intron detention tightly regulates the stemness/differentiation switch in the adult neurogenic niche |
| title_full_unstemmed | Intron detention tightly regulates the stemness/differentiation switch in the adult neurogenic niche |
| title_short | Intron detention tightly regulates the stemness/differentiation switch in the adult neurogenic niche |
| title_sort | intron detention tightly regulates the stemness differentiation switch in the adult neurogenic niche |
| url | https://doi.org/10.1038/s41467-024-47092-z |
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