CTDP1 and RPB7 stabilize and license Pol II termination to reinitiation

The regulation of the transcription process has been investigated extensively, but how RNA Pol II terminates and reinitiates a new round remains elusive. Here, we employed mathematic modeling and time series sequencing to reveal that CTDP1 serves as a crucial regulator of Pol II termination-reinitiation recycling in mammalian cells. Mechanistically, RPB7 recruits CTDP1 to Pol II, where CTDP1 dephosphorylates Pol II. The phosphatase activity of CTDP1 is required for Pol II recycling. Then, RPB7 permits the hypophosphorylated Pol II to reinitiate transcription at gene promoters. The stability of recycling Pol II depends on the incorporation of RPB7, phosphorylation, CTD, the linker region of RPB1, and regulated by the E3 ligase Cullin 3. Our findings collectively demonstrate that phosphatase CTDP1 regulates the recycle of Pol II from termination to reinitiation by interacting with RPB7, potentially serving as a checkpoint for completing Pol II CTD phosphorylation-coupled RNA processing.
In this dataset, the raw data of Western blot, genotyping and imaging in our study was uploaded. The file name has the corresponding figure number in the paper with the detected protein's name (for Western blot) or its treatment condition. For cell imaging, images were acquired by Nikon A1R microscope. More details can be found in our paper.