CDK11 in TREX/THOC Regulates HIV mRNA 3′ End Processing

•The cyclin-dependent kinase CDK11 increases HIV gene expression as part of TREX/THOC•CDK11 is recruited by TREX/THOC to elongating RNAPII and phosphorylates its CTD•RNAPII phosphorylation by CDK11 promotes cleavage and polyadenylation factor recruitment•CDK11 regulates proper 3′ end processing of HIV for optimal viral gene expression

SummaryTranscriptional 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.

Graphical AbstractFigure optionsDownload full-size imageDownload high-quality image (216 K)Download as PowerPoint slide