@article{e0874e726119441fa365c118f6de1716,
title = "Chemical genetics and proteome-wide site mapping reveal cysteine MARylation by PARP-7 on immune-relevant protein targets",
abstract = "Poly(ADP-ribose) polymerase 7 (PARP-7) has emerged as a critically important member of a large enzyme family that catalyzes ADP-ribosylation in mammalian cells. PARP-7 is a critical regulator of the innate immune response. What remains unclear is the mechanism by which PARP-7 regulates this process, namely because the protein targets of PARP-7 mono-ADP-ribosylation (MARylation) are largely unknown. Here, we combine chemical genetics, proximity labeling, and proteome-wide amino acid ADP-ribosylation site profiling for identifying the direct targets and sites of PARP-7-mediated MARylation in a cellular context. We found that the inactive PARP family member, PARP-13—a critical regulator of the antiviral innate immune response—is a major target of PARP-7. PARP-13 is preferentially MARylated on cysteine residues in its RNA binding zinc finger domain. Proteome-wide ADP-ribosylation analysis reveals cysteine as a major MARylation acceptor of PARP-7. This study provides insight into PARP-7 targeting and MARylation site preference.",
author = "Rodriguez, {Kelsie M.} and Buch-Larsen, {Sara C.} and Kirby, {Ilsa T.} and Siordia, {Ivan Rodriguez} and David Hutin and Marit Rasmussen and Grant, {Denis M.} and David, {Larry L.} and Jason Matthews and Nielsen, {Michael L.} and Cohen, {Michael S.}",
note = "Funding Information: We thank John Klimek and Philip Wilmarth for assistance with the CG and BioID MS analysis at the OHSU proteomics core. Mass spectrometry analysis performed by the OHSU Proteomics Shared Resource was partially supported by NIH grants P30EY010572, P30CA069533, and S10OD012246. We thank current and past members of the Cohen lab for many fruitful discussions regarding the experimental design, data analysis, and the preparation of the manuscript. We thank Jonas Damgaard Elsborg for writing the python script used for generation of background sequences for motif analyses, and Ivo Alexander Hendriks for fruitful discussions and help with data analysis of EThcD MS data. We thank Prof. W. Lee Kraus for sharing their PARP-7 chemical genetic studies prior to publication. We thank Prof. Michael O. Hottiger for the PARG plasmid. We thank Prof. Ian Carter-O{\textquoteright}Connell for the SUMO-PARP-13.2 plasmid. This work was funded by the NIH (NIH 2R01NS088629) and the Pew Foundation to M.S.C. Funding Information: OHSU Proteomics Shared Resource was partially supported by NIH grants Funding Information: PARP-13.2 plasmid. This work was funded by the NIH (NIH 2R01NS088629) and the Publisher Copyright: {\textcopyright} 2021, eLife Sciences Publications Ltd. All rights reserved.",
year = "2021",
month = jan,
doi = "10.7554/eLife.60480",
language = "English (US)",
volume = "10",
pages = "1--94",
journal = "eLife",
issn = "2050-084X",
publisher = "eLife Sciences Publications",
}