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Loss of Quaking RNA binding protein disrupts the expression of genes associated with astrocyte maturation in mouse brain.
Sakers, Kristina; Liu, Yating; Llaci, Lorida; Lee, Scott M; Vasek, Michael J; Rieger, Michael A; Brophy, Sean; Tycksen, Eric; Lewis, Renate; Maloney, Susan E; Dougherty, Joseph D.
Afiliación
  • Sakers K; Department of Genetics, Washington University School of Medicine, Saint Louis, MO, 63110, USA.
  • Liu Y; Department of Psychiatry, Washington University School of Medicine, Saint Louis, MO, USA.
  • Llaci L; Department of Genetics, Washington University School of Medicine, Saint Louis, MO, 63110, USA.
  • Lee SM; Department of Psychiatry, Washington University School of Medicine, Saint Louis, MO, USA.
  • Vasek MJ; Division of Biomedical and Biological Sciences, Washington University School of Medicine, Saint Louis, MO, USA.
  • Rieger MA; Department of Genetics, Washington University School of Medicine, Saint Louis, MO, 63110, USA.
  • Brophy S; Department of Psychiatry, Washington University School of Medicine, Saint Louis, MO, USA.
  • Tycksen E; Department of Genetics, Washington University School of Medicine, Saint Louis, MO, 63110, USA.
  • Lewis R; Department of Psychiatry, Washington University School of Medicine, Saint Louis, MO, USA.
  • Maloney SE; Department of Genetics, Washington University School of Medicine, Saint Louis, MO, 63110, USA.
  • Dougherty JD; Department of Psychiatry, Washington University School of Medicine, Saint Louis, MO, USA.
Nat Commun ; 12(1): 1537, 2021 03 09.
Article en En | MEDLINE | ID: mdl-33750804
Quaking RNA binding protein (QKI) is essential for oligodendrocyte development as myelination requires myelin basic protein mRNA regulation and localization by the cytoplasmic isoforms (e.g., QKI-6). QKI-6 is also highly expressed in astrocytes, which were recently demonstrated to have regulated mRNA localization. Here, we define the targets of QKI in the mouse brain via CLIPseq and we show that QKI-6 binds 3'UTRs of a subset of astrocytic mRNAs. Binding is also enriched near stop codons, mediated partially by QKI-binding motifs (QBMs), yet spreads to adjacent sequences. Using a viral approach for mosaic, astrocyte-specific gene mutation with simultaneous translating RNA sequencing (CRISPR-TRAPseq), we profile ribosome associated mRNA from QKI-null astrocytes in the mouse brain. This demonstrates a role for QKI in stabilizing CLIP-defined direct targets in astrocytes in vivo and further shows that QKI mutation disrupts the transcriptional changes for a discrete subset of genes associated with astrocyte maturation.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Encéfalo / Astrocitos / Proteínas de Unión al ARN Tipo de estudio: Risk_factors_studies Límite: Animals Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Encéfalo / Astrocitos / Proteínas de Unión al ARN Tipo de estudio: Risk_factors_studies Límite: Animals Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido