The Integrator complex controls the termination of transcription at diverse classes of gene targets  

作　　者：Jeffrey R Skaar Andrea L Ferris Xiaolin Wu Anita Saraf Kum Kum Khanna Laurence Florens Michael P Washburn Stephen H Hughes Michele Pagano 

机构地区：[1]1Department of Pathology, Laura and lsaac Perlmutter Cancer Center, New York University School of Medicine, 522 First Avenue, New York, NY 10016, USA [2]Howard Hughes Medical Institute, 522 First Avenue New York, NY 10016, USA [3]HIV Drug Resistance Program, National Cancer Institute, Frederick, MD 21702, USA [4]Cancer Research Technology Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA [5]The Stowers Institute for Medical Research, Kansas City, MO 6411, USA [6]QIMR Berghofer Medical Research Institute, Herston, Brisbane, Queensland 4006, Australia [7]Department of Pathology and Laboratory Medicine, The University of Kansas Medical Center, Kansas City, KS 66160, USA

出　　处：《Cell Research》2015年第3期288-305,共18页细胞研究（英文版）

摘　　要：Complexes containing INTS3 and either NABP1 or NABP2 were initially characterized in DNA damage responses, but their biochemical function remained unknown. Using affinity purifications and HIV Integration targeting-se- quencing （HIT-Seq）, we find that these complexes are part of the Integrator complex, which binds RNA Polymerase II and regulates specific target genes. Integrator cleaves snRNAs as part of their processing to their mature form in a mechanism that is intimately coupled with transcription termination. However, HIT-Seq reveals that Integrator also binds to the 3＇ end of replication-dependent histones and promoter proximal regions of genes with polyadenylated transcripts. Depletion of Integrator subunits results in transcription termination failure, disruption of histone mRNA processing, and polyadenylation of snRNAs and histone mRNAs. Furthermore, promoter proximal binding of Inte- grator negatively regulates expression of genes whose transcripts are normally polyadenylated. Integrator recruit- ment to all three gene classes is DSIF-dependent, suggesting that Integrator functions as a termination complex at DSIF-dependent RNA Polymerase II pause sites.

关 键 词：INTEGRATOR SNRNA HISTONE TERMINATION RNA Polyermase II processing 

分 类 号：Q550.2[生物学—生物化学] TN713[电子电信—电路与系统]