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CDK7 inhibition suppresses RNA polymerase II re-initiation and triggers degradation of elongation and 3'-end processing factors

ABSTRACT: CDK7 regulates RNA polymerase II (RNAPII) initiation, elongation, and termination through incompletely-defined mechanisms. Biochemical reconstitution of RNAPII transcription initiation showed that CDK7 inhibition suppressed RNAPII activity by blocking promoter escape and re-initiation and this was Mediator- and TFIID-dependent. These in vitro results were consistent with genomics and transcriptomics experiments in human cells; CDK7 inhibition globally reduced transcription and increased RNAPII promoter-proximal pausing. Moreover, we observed termination defects in CDK7-inhibited cells; unexpectedly, this coincided with rapid, widespread degradation of elongation and 3'-end processing factors. Collectively, these mechanistic insights further define how CDK7 kinase activity regulates RNAPII initiation, termination, and RNA processing.

ORGANISM(S): Homo sapiens

PROVIDER: GSE268531 | GEO | 2024/12/19

REPOSITORIES: GEO

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CDK7 kinase activity promotes RNA polymerase II promoter escape by facilitating initiation factor release

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