Journal
SCIENCE
Volume 349, Issue 6250, Pages 868-873Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.aaa8381
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Funding
- Natural Sciences and Engineering Research Council of Canada
- European Molecular Biology Organization
- Ontario Institute for Regenerative Medicine
- Human Frontier Science Program
- Canadian Institutes of Health Research
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Alternative splicing (AS) generates extensive transcriptomic and proteomic complexity. However, the functions of species-and lineage-specific splice variants are largely unknown. Here we show that mammalian-specific skipping of polypyrimidine tract-binding protein 1 (PTBP1) exon 9 alters the splicing regulatory activities of PTBP1 and affects the inclusion levels of numerous exons. During neurogenesis, skipping of exon 9 reduces PTBP1 repressive activity so as to facilitate activation of a brain-specific AS program. Engineered skipping of the orthologous exon in chicken cells induces a large number of mammalian-like AS changes in PTBP1 target exons. These results thus reveal that a single exon-skipping event in an RNA binding regulator directs numerous AS changes between species. Our results further suggest that these changes contributed to evolutionary differences in the formation of vertebrate nervous systems.
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