Redundant pathways for removal of defective RNA polymerase II complexes at a promoter-proximal pause checkpoint.

ABSTRACT: The biological purpose of Integrator and RNA polymerase II (RNAPII) promoter-proximal pausing remains uncertain. Here, we show that loss of INTS6 in human cells results in increased interaction of RNAPII with proteins that can mediate its dissociation from the DNA template, including the CRL3^ARMC5 E3 ligase, which ubiquitylates CTD serine₅-phosphorylated RPB1 for degradation. ARMC5-dependent RNAPII ubiquitylation is activated by defects in factors acting at the promoter-proximal pause, including Integrator, DSIF, and capping enzyme. This ARMC5 checkpoint normally curtails a sizeable fraction of RNAPII transcription, and ARMC5 knockout cells produce more uncapped transcripts. When both the Integrator and CRL3^ARMC5 turnover mechanisms are compromised, cell gr

SUBMITTER: Blears D 

PROVIDER: S-EPMC11663130 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature