CTDP1 and RPB7 Stabilize Pol II and Permit Reinitiation

The mechanisms governing the termination and subsequent reinitiation of RNA polymerase II (Pol II) remain poorly understood. Here we found that depletion of RPB7 leads to the destabilization of Pol II’s largest subunit, RPB1. This destabilization is influenced by the loop regions of RPB7, CDK9, the C-terminal domain (CTD) of RPB1, and its linker region. The stabilization process of RPB1 is regulated by the E3 ubiquitin ligase Cullin 3. Additionally, RPB7 interacts with the phosphatase CTDP1, which is crucial for maintaining RPB1 stability. RPB7 is also vital for the reinitiation of Pol II, engages with RNA processing factors, and is localized to the RNA exit channel of the Pol II complex. The absence of RPB7 compromises RNA processing. We propose that RPB7 recruits CTDP1 to dephosphorylate Pol II, enhancing its stability and facilitating efficient reinitiation, adding a new dimension to transcriptional regulation.