Publication Date:
2015-08-22
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gueroussov, Serge -- Gonatopoulos-Pournatzis, Thomas -- Irimia, Manuel -- Raj, Bushra -- Lin, Zhen-Yuan -- Gingras, Anne-Claude -- Blencowe, Benjamin J -- Canadian Institutes of Health Research/Canada -- New York, N.Y. -- Science. 2015 Aug 21;349(6250):868-73. doi: 10.1126/science.aaa8381.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Donnelly Centre, University of Toronto, Toronto, Ontario M5S 3E1, Canada. Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 1A8, Canada. ; Donnelly Centre, University of Toronto, Toronto, Ontario M5S 3E1, Canada. ; Donnelly Centre, University of Toronto, Toronto, Ontario M5S 3E1, Canada. EMBL/CRG Systems Biology Research Unit, Centre for Genomic Regulation (CRG), Dr. Aiguader 88, 08003 Barcelona, Spain. ; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, Ontario M5G 1X5, Canada. ; Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 1A8, Canada. Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, Ontario M5G 1X5, Canada. ; Donnelly Centre, University of Toronto, Toronto, Ontario M5S 3E1, Canada. Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 1A8, Canada. b.blencowe@utoronto.ca.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26293963" target="_blank"〉PubMed〈/a〉
Keywords:
*Alternative Splicing
;
Animals
;
*Biological Evolution
;
Brain/*embryology
;
Chickens
;
Embryonic Stem Cells/metabolism
;
Exons/genetics
;
HEK293 Cells
;
Heterogeneous-Nuclear Ribonucleoproteins/*genetics
;
Humans
;
Mice
;
Neural Stem Cells/metabolism
;
Neurogenesis/*genetics
;
Polypyrimidine Tract-Binding Protein/*genetics
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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