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 find 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 an emerging dimension to transcriptional regulation.

目前人们对RNA聚合酶II（RNA polymerase II，Pol II）的终止及后续再起始机制仍知之甚少。本研究发现，RPB7的耗竭会导致Pol II最大亚基RPB1的不稳定。该不稳定现象受RPB7、CDK9的环区，以及RPB1的C端结构域（C-terminal domain，CTD）及其连接区的调控。RPB1的稳定过程受E3泛素连接酶（E3 ubiquitin ligase）Cullin 3的调控。此外，RPB7可与磷酸酶CTDP1相互作用，该作用对维持RPB1的稳定性至关重要。RPB7对Pol II的再起始过程同样至关重要，它可与RNA加工因子结合，并定位于Pol II复合物的RNA出口通道。RPB7的缺失会损害RNA加工过程。本研究提出，RPB7可招募CTDP1对Pol II进行去磷酸化修饰，从而增强其稳定性并促进高效再起始，为转录调控研究增添了全新的维度。