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

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

Bloomberg School of Public Health

Research output: Contribution to journal › Article › peer-review

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.

Original language	English (US)
Article number	3
Journal	Cell Discovery
Volume	8
Issue number	1
DOIs	https://doi.org/10.1038/s41421-021-00355-1
State	Published - Dec 2022

ASJC Scopus subject areas

Biochemistry
Molecular Biology
Genetics
Cell Biology

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10.1038/s41421-021-00355-1

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title = "Truncated PARP1 mediates ADP-ribosylation of RNA polymerase III for apoptosis",

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.",

author = "Qian Chen and Kai Ma and Xiuhua Liu and Chen, {Shih Hsun} and Peng Li and Yonghao Yu and Leung, {Anthony K.L.} and Xiaochun Yu",

note = "Funding Information: We thank Dr. Kate Fitzgerald, Dr. Anthony R. Fehr, and Dr. Christopher S. Sullivan for invaluable reagents. We are thankful to Dr. Michael L. Nielsen at the University of Copenhagen for database searching. This work was supported in part by grants from the National Natural Science Foundation of China (32090034 and 81874160), Westlake University Education Foundation, and Westlake Laboratory of Life Sciences and Biomedicine. Publisher Copyright: {\textcopyright} 2021, The Author(s).",

year = "2022",

month = dec,

doi = "10.1038/s41421-021-00355-1",

language = "English (US)",

volume = "8",

journal = "Cell Discovery",

issn = "2056-5968",

publisher = "Nature Publishing Group",

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T1 - Truncated PARP1 mediates ADP-ribosylation of RNA polymerase III for apoptosis

AU - Chen, Qian

AU - Ma, Kai

AU - Liu, Xiuhua

AU - Chen, Shih Hsun

AU - Li, Peng

AU - Yu, Yonghao

AU - Leung, Anthony K.L.

AU - Yu, Xiaochun

N1 - Funding Information: We thank Dr. Kate Fitzgerald, Dr. Anthony R. Fehr, and Dr. Christopher S. Sullivan for invaluable reagents. We are thankful to Dr. Michael L. Nielsen at the University of Copenhagen for database searching. This work was supported in part by grants from the National Natural Science Foundation of China (32090034 and 81874160), Westlake University Education Foundation, and Westlake Laboratory of Life Sciences and Biomedicine. Publisher Copyright: © 2021, The Author(s).

PY - 2022/12

Y1 - 2022/12

N2 - 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.

AB - 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.

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

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