TY - JOUR
T1 - Regulation of alternative splicing through coupling with transcription and chromatin structure
AU - Naftelberg, Shiran
AU - Schor, Ignacio E.
AU - Ast, Gil
AU - Kornblihtt, Alberto R.
N1 - Publisher Copyright:
Copyright © 2015 by Annual Reviews. All rights reserved.
PY - 2015/6/2
Y1 - 2015/6/2
N2 - 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.
AB - 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.
KW - Alternative splicing
KW - Chromatin organization
KW - Histone modifications
KW - Molecular evolution
KW - Nucleosome positioning
KW - Transcription
UR - http://www.scopus.com/inward/record.url?scp=84930716439&partnerID=8YFLogxK
U2 - 10.1146/annurev-biochem-060614-034242
DO - 10.1146/annurev-biochem-060614-034242
M3 - סקירה
C2 - 26034889
AN - SCOPUS:84930716439
VL - 84
SP - 165
EP - 198
JO - Annual Review of Biochemistry
JF - Annual Review of Biochemistry
SN - 0066-4154
ER -