The Integrator complex controls the termination of transcription at diverse classes of gene targets
Year: 2015
Type: article
Abstract: 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-sequencing (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 Integrator negatively regulates expression of genes whose transcripts are normally polyadenylated. Integrator recruitment to all three gene classes is DSIF-dependent, suggesting that Integrator functions as a termination complex at DSIF-dependent RNA Polymerase II pause sites.
Source: Cell Research
DOI: 10.1038/cr.2015.19
Institutions: NYU Langone’s Laura and Isaac Perlmutter Cancer Center, New York University, National Cancer Institute, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research Inc. (United States), Stowers Institute for Medical Research, QIMR Berghofer Medical Research Institute, University of Kansas Medical Center, Howard Hughes Medical Institute
Language: English
Topic: RNA Research and Splicing
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $5,190
Funders: American Cancer Society, Stowers Institute for Medical Research, Frederick National Laboratory for Cancer Research, National Institutes of Health, Medical Research Council, National Health and Medical Research Council, National Cancer Institute, National Institute of General Medical Sciences
Awards: Regulation of the cell cycle by CRL ubiquitin ligases, G3503792436, G3549828030, G386607036, Role of the SCF/Fbxo15 ubiquitin ligase in stem cells and cancer biology, G4988656331, G5888954722, Molecular, Oncology and Immunology Training Grant, F-box proteins: deregulated cell cycle control and proteolysis in cancer, G9000113513, G9000135018, G9000281995, G9000296953, Cancer Center Support Grant
OpenAlex ID: W2033997312