Chemical genetics and proteome-wide site mapping reveal cysteine MARylation by PARP-7 on immune-relevant protein targets
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Chemical genetics and proteome-wide site mapping reveal cysteine MARylation by PARP-7 on immune-relevant protein targets. / Rodriguez, Kelsie M.; Buch-Larsen, Sara C.; Kirby, Ilsa T.; Siordia, Ivan Rodriguez; Hutin, David; Rasmussen, Marit; Grant, Denis M.; David, Larry L.; Matthews, Jason; Nielsen, Michael L.; Cohen, Michael S.
In: eLife, Vol. 10, e60480, 2021.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Chemical genetics and proteome-wide site mapping reveal cysteine MARylation by PARP-7 on immune-relevant protein targets
AU - Rodriguez, Kelsie M.
AU - Buch-Larsen, Sara C.
AU - Kirby, Ilsa T.
AU - Siordia, Ivan Rodriguez
AU - Hutin, David
AU - Rasmussen, Marit
AU - Grant, Denis M.
AU - David, Larry L.
AU - Matthews, Jason
AU - Nielsen, Michael L.
AU - Cohen, Michael S.
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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.
U2 - 10.7554/eLife.60480
DO - 10.7554/eLife.60480
M3 - Journal article
C2 - 33475084
AN - SCOPUS:85100154907
VL - 10
JO - eLife
JF - eLife
SN - 2050-084X
M1 - e60480
ER -
ID: 258778359