CDK12/13 promote splicing of proximal introns by enhancing the interaction between RNA polymerase II and the splicing factor SF3B1.

ABSTRACT: Transcription-associated cyclin-dependent kinases (CDKs) regulate the transcription cycle through sequential phosphorylation of RNA polymerase II (RNAPII). Herein, we report that dual inhibition of the highly homologous CDK12 and CDK13 impairs splicing of a subset of promoter-proximal introns characterized by weak 3' splice sites located at larger distance from the branchpoint. Nascent transcript analysis indicated that these introns are selectively retained upon pharmacological inhibition of CDK12/13 with respect to downstream introns of the same pre-mRNAs. Retention of these introns was also triggered by pladienolide B (PdB), an inhibitor of the U2 small nucelar ribonucleoprotein (snRNP) factor SF3B1 that recognizes the branchpoint. CDK12/13 activity promotes the interaction of SF3B1 wit

SUBMITTER: Panzeri V 

PROVIDER: S-EPMC10287901 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature