title: Regulation of alternative splicing through coupling with transcription and chromatin structure.
abstract: 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 important as regulation of transcription to determine cell- and tissue-specific features, normal cell functioning, and responses of eukaryotic cells to external 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 structure, 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 recruitment of splicing factors and adaptor proteins to chromatin components act in coordination to regulate alternative splicing.
authors.affiliation: Sackler Medical School, Tel Aviv University, Tel Aviv 69978, Israel; email: gilast@post.tau.ac.il.
authors.forename: Shiran
authors.initials: S
authors.lastname: Naftelberg
authors.forename: Ignacio E
authors.initials: IE
authors.lastname: Schor
authors.forename: Gil
authors.initials: G
authors.lastname: Ast
authors.forename: Alberto R
authors.initials: AR
authors.lastname: Kornblihtt
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D002843:Chromatin / Q000378:metabolism*; D019175:DNA Methylation; D005786:Gene Expression Regulation; D006657:Histones / Q000378:metabolism; D006801:Humans; D008957:Models, Genetic; D009707:Nucleosomes / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D014158:Transcription, Genetic
chemical_list: D002843:Chromatin; D006657:Histones; D009707:Nucleosomes
keywords: alternative splicing; chromatin organization; histone modifications; molecular evolution; nucleosome positioning; transcription