Regulation of alternative splicing through coupling with transcription and chromatin structure

NAFTELBERG, SHIRAN; SCHOR, IGNACIO; AST, GIL; KORNBLIHTT, ALBERTO

ANNUAL REVIEW OF BIOCHEMISTRY

ANNUAL REVIEWS

Año: 2015 vol. 84 p. 165 - 198

0066-4154

Alternative precursor messenger RNA (pre-mRNA) splicing plays a pivotal role in the flow of genetic information from DNA to proteins by expanding the coding capacity of genomes. Regulation of alternative splicing is as im- portant as regulation of transcription to determine cell- and tissue-specific features, normal cell functioning, and responses of eukaryotic cells to exter- nal cues. Its importance is confirmed by the evolutionary conservation and diversification of alternative splicing and the fact that its deregulation causes hereditary disease and cancer. This review discusses the multiple layers of cotranscriptional regulation of alternative splicing in which chromatin struc- ture, DNA methylation, histone marks, and nucleosome positioning play a fundamental role in providing a dynamic scaffold for interactions between the splicing and transcription machineries. We focus on evidence for how the kinetics of RNA polymerase II (RNAPII) elongation and the recruit- ment of splicing factors and adaptor proteins to chromatin components act in coordination to regulate alternative splicing.