SRSF1 regulates the formation of the Brd4/P-TEFb complex.
Positive transcription elongation factor P-TEFb, which consists of CDK9 and CycT1, modulates transcriptional elongation by alternating between an inactive and an active complex state. This state transition is strictly controlled by several closely interconnected steps that begin with the release of P-TEFb from the inactive 7SK snRNP complex in the nucleoplasm, followed by reassembly of active P-TEFb and functional restart of paused transcriptional elongation on chromatin. Our previous work has elucidated the mechanisms underlying HMBA-induced P-TEFb release and subsequent functional restart of transcriptional elongation. Here, we identify that HMBA-stimulated SRSF1 regulates the assembly of the active Brd4/P-TEFb complex to enable productive transcriptional elongation.