title: CDK11 in TREX/THOC Regulates HIV mRNA 3' End Processing.
abstract: Transcriptional cyclin-dependent kinases play important roles in eukaryotic gene expression. CDK7, CDK9 (P-TEFb), and CDK13 are also critical for HIV replication. However, the function of CDK11 remained enigmatic. In this report, we determined that CDK11 regulates the cleavage and polyadenylation (CPA) of all viral transcripts. CDK11 was found associated with the TREX/THOC, which recruited this kinase to DNA. Once at the viral genome, CDK11 phosphorylated serines at position 2 in the CTD of RNAPII, which increased levels of CPA factors at the HIV 3' end. In its absence, cleavage of viral transcripts was greatly attenuated. In contrast, higher levels of CDK11 increased the length of HIV poly(A) tails and the stability of mature viral transcripts. We conclude that CDK11 plays a critical role for the cotranscriptional processing of all HIV mRNA species.
authors.affiliation: Departments of Medicine, Microbiology, and Immunology, University of California at San Francisco, San Francisco, CA 94143, USA.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Pak
authors.affiliation: Departments of Medicine, Microbiology, and Immunology, University of California at San Francisco, San Francisco, CA 94143, USA.
authors.forename: Tristan T
authors.initials: TT
authors.lastname: Eifler
authors.affiliation: Department of Cellular and Molecular Pharmacology, University of California at San Francisco, San Francisco, CA 94143, USA; Gladstone Institutes, San Francisco, CA, 94143, USA.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Jäger
authors.affiliation: Department of Cellular and Molecular Pharmacology, University of California at San Francisco, San Francisco, CA 94143, USA; Gladstone Institutes, San Francisco, CA, 94143, USA.
authors.forename: Nevan J
authors.initials: NJ
authors.lastname: Krogan
authors.affiliation: Departments of Medicine, Microbiology, and Immunology, University of California at San Francisco, San Francisco, CA 94143, USA.
authors.forename: Koh
authors.initials: K
authors.lastname: Fujinaga
authors.affiliation: Departments of Medicine, Microbiology, and Immunology, University of California at San Francisco, San Francisco, CA 94143, USA. Electronic address: matija.peterlin@ucsf.edu.
authors.forename: B Matija
authors.initials: BM
authors.lastname: Peterlin
mesh_terms: D018797:Cell Cycle Proteins / Q000378:metabolism*; D018844:Cyclin-Dependent Kinases / Q000235:genetics*; D004268:DNA-Binding Proteins; D005090:Exodeoxyribonucleases / Q000378:metabolism*; D057809:HEK293 Cells; D006678:HIV / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D019169:Jurkat Cells; D009687:Nuclear Proteins / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D026723:Polyadenylation; D026721:RNA 3' End Processing; D016601:RNA-Binding Proteins
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; D016601:RNA-Binding Proteins; C400546:THOC1 protein, human; C447612:CDK11a protein, human; D018844:Cyclin-Dependent Kinases; D005090:Exodeoxyribonucleases; C429526:three prime repair exonuclease 1