Resumen
Poly(ADP-ribose) polymerases (PARPs) are abundant nuclear proteins that synthesize ADP ribose polymers (pADPr) and catalyze the addition of (p)ADPr to target biomolecules. PARP1, the most abundant and well-studied PARP, is a multifunctional enzyme that participates in numerous critical cellular processes. A considerable amount of PARP research has focused on PARP1's role in DNA damage. However, an increasing body of evidence outlines more routine roles for PARP and PARylation in nearly every step of RNA biogenesis and metabolism. PARP1's involvement in these RNA processes is pleiotropic and has been ascribed to PARP1's unique flexible domain structures. PARP1 domains are modular self-arranged enabling it to recognize structurally diverse substrates and to act simultaneously through multiple discrete mechanisms. These mechanisms include direct PARP1-protein binding, PARP1-nucleic acid binding, covalent PARylation of target molecules, covalent autoPARylation, and induction of noncovalent interactions with PAR molecules. A combination of these mechanisms has been implicated in PARP1's context-specific regulation of RNA biogenesis and metabolism. We examine the mechanisms of PARP1 regulation in transcription initiation, elongation and termination, co-transcriptional splicing, RNA export, and post-transcriptional RNA processing. Finally, we consider promising new investigative avenues for PARP1 involvement in these processes with an emphasis on PARP1 regulation of subcellular condensates. This article is categorized under: RNA Processing > Splicing Regulation/Alternative Splicing.
| Idioma original | English |
|---|---|
| Número de artículo | e1617 |
| Publicación | Wiley Interdisciplinary Reviews: RNA |
| Volumen | 12 |
| N.º | 2 |
| DOI | |
| Estado | Published - mar 1 2021 |
Nota bibliográfica
Publisher Copyright:© 2020 The Authors. WIREs RNA published by Wiley Periodicals LLC.
Financiación
We would like to thank the members of the Fondue\u2010Mittendorf laboratory for critical reading of the manuscript. We would also like to thank the Markey Cancer Center's Research Communications Office for manuscript editing (P30 CA177558). Research reported in this publication was supported by the National Institutes of Environmental Health grant R01 ES024478 (Y. F. N.\u2010M.), National Science Foundation grant MCB 1517986 (Y. F. N.\u2010M.), and GRF 1839289 (R. E.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIEHS or NSF. We would like to thank the members of the Fondue-Mittendorf laboratory for critical reading of the manuscript. We would also like to thank the Markey Cancer Center's Research Communications Office for manuscript editing (P30 CA177558). Research reported in this publication was supported by the National Institutes of Environmental Health grant R01 ES024478 (Y. F. N.-M.), National Science Foundation grant MCB 1517986 (Y. F. N.-M.), and GRF 1839289 (R. E.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIEHS or NSF.
| Financiadores | Número del financiador |
|---|---|
| No añadido | MCB 1517986, 1517986, 1839289 |
| National Institutes of Health/National Institute of Environmental Health Sciences | R01ES024478, R01ES031846 |
| National Childhood Cancer Registry – National Cancer Institute | P30CA177558 |
| University of Kentucky Markey Cancer Center | P30 CA177558 |
| National Institutes of Health/National Institute of Environmental Health Sciences | R01 ES024478 |
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology