STAU2 binds a complex RNA cargo that changes temporally with production of diverse intermediate progenitor cells during mouse corticogenesis

Rebecca Chowdhury, Yue Wang, Melissa Campbell, Susan K. Goderie, Francis Doyle, Scott A. Tenenbaum, Gretchen Kusek, Thomas R. Kiehl, Suraiya A. Ansari, Nathan C. Boles, Sally Temple

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

STAU2 is a double-stranded RNA-binding protein enriched in the nervous system. During asymmetric divisions in the developing mouse cortex, STAU2 preferentially distributes into the intermediate progenitor cell (IPC), delivering RNA molecules that can impact IPC behavior. Corticogenesis occurs on a precise time schedule, raising the hypothesis that the cargo STAU2 delivers into IPCs changes over time. To test this, we combine RNA-immunoprecipitation with sequencing (RIP-seq) over four stages of mouse cortical development, generating a comprehensive cargo profile for STAU2. A subset of the cargo was ‘stable’, present at all stages, and involved in chromosome organization, macromolecule localization, translation and DNA repair. Another subset was ‘dynamic’, changing with cortical stage, and involved in neurogenesis, cell projection organization, neurite outgrowth, and included cortical layer markers. Notably, the dynamic STAU2 cargo included determinants of IPC versus neuronal fates and genes contributing to abnormal corticogenesis. Knockdown of one STAU2 target, Taf13, previously linked to microcephaly and impaired myelination, reduced oligodendrogenesis in vitro. We conclude that STAU2 contributes to the timing of corticogenesis by binding and delivering complex and temporally regulated RNA cargo into IPCs.

Original languageEnglish
Article numberdev199376
JournalDevelopment (Cambridge)
Volume148
Issue number15
DOIs
Publication statusPublished - Aug 2021

Keywords

  • Cerebral cortex
  • Intermediate progenitor cells
  • Mouse
  • RIP-seq
  • RNA-binding protein
  • STAU2

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

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