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Cell Host Microbe. 2015 Nov 11;18(5):560-70. doi: 10.1016/j.chom.2015.10.012.

CDK11 in TREX/THOC Regulates HIV mRNA 3' End Processing.

Author information

1
Departments of Medicine, Microbiology, and Immunology, University of California at San Francisco, San Francisco, CA 94143, USA.
2
Department of Cellular and Molecular Pharmacology, University of California at San Francisco, San Francisco, CA 94143, USA; Gladstone Institutes, San Francisco, CA, 94143, USA.
3
Departments of Medicine, Microbiology, and Immunology, University of California at San Francisco, San Francisco, CA 94143, USA. Electronic address: matija.peterlin@ucsf.edu.

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.

PMID:
26567509
PMCID:
PMC4648707
DOI:
10.1016/j.chom.2015.10.012
[Indexed for MEDLINE]
Free PMC Article

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