Identification of Integrator-PP2A complex (INTAC), an RNA polymerase II phosphatase

Author:

Zheng Hai12ORCID,Qi Yilun1ORCID,Hu Shibin1ORCID,Cao Xuan3ORCID,Xu Congling1ORCID,Yin Zhinang4ORCID,Chen Xizi1ORCID,Li Yan1ORCID,Liu Weida1ORCID,Li Jie1,Wang Jiawei5ORCID,Wei Gang3ORCID,Liang Kaiwei4ORCID,Chen Fei Xavier1ORCID,Xu Yanhui126ORCID

Affiliation:

1. Fudan University Shanghai Cancer Center, Institutes of Biomedical Sciences, State Key Laboratory of Genetic Engineering and Shanghai Key Laboratory of Medical Epigenetics, Shanghai Medical College of Fudan University, Shanghai 200032, China.

2. The International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, China, Department of Systems Biology for Medicine, School of Basic Medical Sciences, Shanghai Medical College of Fudan University, Shanghai 200032, China.

3. CAS Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.

4. Department of Pathophysiology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China.

5. State Key Laboratory of Membrane Biology, Beijing Advanced Innovation Center for Structural Biology, School of Life Sciences, Tsinghua University, 100084 Beijing, China.

6. Human Phenome Institute, Collaborative Innovation Center of Genetics and Development, School of Life Sciences, Fudan University, Shanghai 200433, China.

Abstract

Dephosphorylating RNA polymerase II Transcription in metazoans requires coordination of multiple factors to control the progression of polymerases and the integrity of their RNA products. Zheng et al. identified a new dual-enzyme complex called INTAC, which is composed of protein phosphatase 2A (PP2A) core enzyme and the multisubunit RNA endonuclease Integrator. Structural and functional studies show that INTAC functions as a noncanonical PP2A holoenzyme that dephosphorylates the C-terminal domain of RNA polymerase II to attenuate transcription. This study provides a direct connection between PP2A-mediated dephosphorylation and transcriptional regulation, two fundamental cellular processes. Science , this issue p. eabb5872

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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