The transcriptional coactivator RUVBL2 regulates Pol II clustering with diverse transcription factors

Hui Wang, Boyuan Li, Linyu Zuo, Bo Wang, Yan Yan, Kai Tian, Rong Zhou, Chenlu Wang, Xizi Chen, Yongpeng Jiang, Haonan Zheng, Fangfei Qin, Bin Zhang, Yang Yu, Chao-Pei Liu, Yanhui Xu, Juntao Gao, Zhi Qi, Wulan Deng and Xiong Ji ()
Additional contact information
Hui Wang: Peking University
Boyuan Li: Peking University
Linyu Zuo: Peking University
Bo Wang: Peking University
Yan Yan: Tsinghua University
Kai Tian: Peking University
Rong Zhou: Peking University
Chenlu Wang: Peking University
Xizi Chen: Fudan University Shanghai Cancer Center, Institutes of Biomedical Sciences, Shanghai Medical College of Fudan University
Yongpeng Jiang: Peking University
Haonan Zheng: Peking University
Fangfei Qin: Peking University
Bin Zhang: University of Rochester Medical Center
Yang Yu: Chinese Academy of Sciences
Chao-Pei Liu: Chinese Academy of Sciences
Yanhui Xu: Fudan University Shanghai Cancer Center, Institutes of Biomedical Sciences, Shanghai Medical College of Fudan University
Juntao Gao: Tsinghua University
Zhi Qi: Peking University
Wulan Deng: Peking University
Xiong Ji: Peking University

Nature Communications, 2022, vol. 13, issue 1, 1-26

Abstract: Abstract RNA polymerase II (Pol II) apparatuses are compartmentalized into transcriptional clusters. Whether protein factors control these clusters remains unknown. In this study, we find that the ATPase-associated with diverse cellular activities (AAA + ) ATPase RUVBL2 co-occupies promoters with Pol II and various transcription factors. RUVBL2 interacts with unphosphorylated Pol II in chromatin to promote RPB1 carboxy-terminal domain (CTD) clustering and transcription initiation. Rapid depletion of RUVBL2 leads to a decrease in the number of Pol II clusters and inhibits nascent RNA synthesis, and tethering RUVBL2 to an active promoter enhances Pol II clustering at the promoter. We also identify target genes that are directly linked to the RUVBL2-Pol II axis. Many of these genes are hallmarks of cancers and encode proteins with diverse cellular functions. Our results demonstrate an emerging activity for RUVBL2 in regulating Pol II cluster formation in the nucleus.

Date: 2022
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DOI: 10.1038/s41467-022-33433-3

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