Regulation of alternative splicing through coupling with transcription and chromatin structure

Shiran Naftelberg, Ignacio E. Schor, Gil Ast, Alberto R. Kornblihtt

Research output: Contribution to journalReview articlepeer-review

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.

Original languageEnglish
Pages (from-to)165-198
Number of pages34
JournalAnnual Review of Biochemistry
Volume84
DOIs
StatePublished - 2 Jun 2015

Keywords

  • Alternative splicing
  • Chromatin organization
  • Histone modifications
  • Molecular evolution
  • Nucleosome positioning
  • Transcription

Fingerprint

Dive into the research topics of 'Regulation of alternative splicing through coupling with transcription and chromatin structure'. Together they form a unique fingerprint.

Cite this