期刊
CELL
卷 159, 期 7, 页码 1511-1523出版社
CELL PRESS
DOI: 10.1016/j.cell.2014.11.035
关键词
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资金
- Canadian Institute of Health Research (CIHR) Postdoctoral Fellowship
- NIMH NRSA fellowship
- Department of Cell and Systems Biology, University of Toronto
- Banting and Best CIHR Scholarship
- EMBO
- OSCI
- CIHR
- Ontario Research Fund
- Alzheimer's Society, Canada
- University of Toronto McLaughlin Centre
- NIH/NHGRI [P50 HG004233, U01HG001715]
- Krembil Foundation
- Avon Foundation
- NIMH [5R37MH060233, 5R01MH094714]
- Simons Foundation [SFARI 206744]
- Canada Excellence Research Chairs Program
Alternative splicing (AS) generates vast transcriptomic and proteomic complexity. However, which of the myriad of detected AS events provide important biological functions is not well understood. Here, we define the largest program of functionally coordinated, neural-regulated AS described to date in mammals. Relative to all other types of AS within this program, 3-15 nucleotide microexons'' display the most striking evolutionary conservation and switch-like regulation. These microexons modulate the function of interaction domains of proteins involved in neurogenesis. Most neural microexons are regulated by the neuronal-specific splicing factor nSR100/SRRM4, through its binding to adjacent intronic enhancer motifs. Neural microexons are frequently misregulated in the brains of individuals with autism spectrum disorder, and this misregulation is associated with reduced levels of nSR100. The results thus reveal a highly conserved program of dynamic microexon regulation associated with the remodeling of protein-interaction networks during neurogenesis, the misregulation of which is linked to autism.
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