Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

An Alternative Splicing Event Amplifies Evolutionary Differences Between Vertebrates

ABSTRACT: 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 exon 9 of PTBP1 alters its splicing regulatory activities 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. The results further suggest that these changes contributed to evolutionary differences in the formation of vertebrate nervous systems. This study contains two sets of samples: (Set 1) mRNA profiling of human 293 cells subjected to four different conditions in two biological replicates: non-targetting control siRNA, PTBP1 and PTBP2 siRNA, PTBP1 and PTBP2 siRNA with overexpression of full-length human PTBP1, PTBP1 and PTBP2 siRNA with overexpression of exon-excluded human PTBP1. (Set 2) mRNA profiling of chicken DT40 cells with 3 genotypes in two bioligcal replicates: wildtype cells, cells with PTBP1 exon 8 (orthologous to human PTBP1 exon 9) deleted in one allele, and cells with PTBP1 exon 8 deleted in both alleles.

ORGANISM(S): Homo sapiens

SUBMITTER: Serge Gueroussov

PROVIDER: E-GEOD-69656 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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An alternative splicing event amplifies evolutionary differences between vertebrates.

Gueroussov Serge S Gonatopoulos-Pournatzis Thomas T Irimia Manuel M Raj Bushra B Lin Zhen-Yuan ZY Gingras Anne-Claude AC Blencowe Benjamin J BJ

Science (New York, N.Y.) 20150801 6250

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 brai ...[more]

PMID: 26293963

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Dataset Information

An Alternative Splicing Event Amplifies Evolutionary Differences Between Vertebrates

Publications

An alternative splicing event amplifies evolutionary differences between vertebrates.

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