Truncated PARP1 mediates ADP-ribosylation of RNA polymerase III for apoptosis

Qian Chen; Kai Ma; Xiuhua Liu; Shih-Hsun Chen; Peng Li; Yonghao Yu; Anthony K L Leung; Xiaochun Yu

doi:10.1038/s41421-021-00355-1

Truncated PARP1 mediates ADP-ribosylation of RNA polymerase III for apoptosis

Cell Discov. 2022 Jan 18;8(1):3. doi: 10.1038/s41421-021-00355-1.

Authors

Qian Chen^#¹, Kai Ma^#², Xiuhua Liu³, Shih-Hsun Chen⁴, Peng Li⁵, Yonghao Yu⁵, Anthony K L Leung^{6

7

8}, Xiaochun Yu^{9

10

11

12}

Affiliations

¹ Department of Cancer Genetics and Epigenetics, Beckman Research Institute, City of Hope Medical Center, Duarte, CA, USA. qian_chen2020@outlook.com.
² Department of Cancer Genetics and Epigenetics, Beckman Research Institute, City of Hope Medical Center, Duarte, CA, USA.
³ College of Life Sciences, Hebei University, Baoding, Hebei, China.
⁴ Institute of Biochemical Sciences, National Taiwan University, Taipei, Taiwan, China.
⁵ Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX, USA.
⁶ Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
⁷ Department of Molecular Biology and Genetics, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
⁸ Department of Oncology, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
⁹ Department of Cancer Genetics and Epigenetics, Beckman Research Institute, City of Hope Medical Center, Duarte, CA, USA. yuxiaochun@westlake.edu.cn.
¹⁰ Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang, China. yuxiaochun@westlake.edu.cn.
¹¹ School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China. yuxiaochun@westlake.edu.cn.
¹² Institute of Basic Medical Sciences, Westlake Institute for Advanced Study, Hangzhou, Zhejiang, China. yuxiaochun@westlake.edu.cn.

^# Contributed equally.

Abstract

Caspase-mediated cleavage of PARP1 is a surrogate marker for apoptosis. However, the biological significance of PARP1 cleavage during apoptosis is still unclear. Here, using unbiased protein affinity purification, we show that truncated PARP1 (tPARP1) recognizes the RNA polymerase III (Pol III) complex in the cytosol. tPARP1 mono-ADP-ribosylates RNA Pol III in vitro and mediates ADP-ribosylation of RNA Pol III during poly(dA-dT)-stimulated apoptosis in cells. tPARP1-mediated activation of RNA Pol III facilitates IFN-β production and apoptosis. In contrast, suppression of PARP1 or expressing the non-cleavable form of PARP1 impairs these molecular events. Taken together, these studies reveal a novel biological role of tPARP1 during cytosolic DNA-induced apoptosis.

Grants and funding

32090034/National Natural Science Foundation of China (National Science Foundation of China)