THOC5 complexes with DDX5, DDX17, and CDK12 to regulate R loop structures and transcription elongation rate

Alternative cleavage and polyadenylation (APA) is a widespread mechanism to generate mRNA isoforms with alternative 3’ untranslated regions (UTRs). The expression of alternative 3’ UTR isoforms is controlled in a gene-specific manner by environmental cues and is dysregulated in cancer. In this study, Polenkowski and colleagues investigated the connection between transcription elongation rate APA and mRNA export using direct RNA sequencing technology.

Publication: Polenkowski, M., Allister, A.B., Burbano de Lara, S., Pierce, A., Geary, B., El Bounkari, O., Wiehlmann, L., Hoffmann, A., Whetton, A.D., Tamura, T., and Tran, D.D.H. (2023). THOC5 complexes with DDX5, DDX17, and CDK12 to regulate R loop structures and transcription elongation rate. iScience 26, 105784.

Figure legend: Novel role of the THOC5/THOC6 complex during transcription elongation. When transcription elongation rate is low and R-loops are formed, the THOC5/THOC6 complex recruits CTD kinase CDK12, which phosphorylates the CTD domain of RNA polymerase II at serine 2 and enhances the elongation. At the same time, the THOC5/THOC6 complex also recruits DNA-RNA helicases DDX5 and DDX17 to resolve the R-loops, thus preventing transcription elongation impairment and premature termination.