The Integrator-PP2A complex integrates promoter-proximal premature termination with chromatin context and genome maintenance.

Well-regulated transcription is essential for maintaining cellular homeostasis and genome integrity. The Integrator-PP2A complex has emerged as a major regulator of transcription by stimulating promoter-proximal termination of RNA polymerase II (Pol II). By employing dual catalytic activities, Integrator-PP2A shapes transcriptional output, limits aberrant RNA production, and suppresses R-loop-associated genome instability. Integrator-PP2A is highly modular, enabling dynamic interactions with transcription factors and epigenetic modifiers in distinct chromatin contexts and serving as a molecular hub that links transcriptional regulation to RNA quality control, chromatin state, and genome surveillance. Here, we review recent insights into the composition, mechanisms, and regulatory functions of this complex, which together establish its broad roles across both coding and noncoding transcriptional programs.