The multifaceted role of PARP1 in RNA biogenesis

Rebekah Eleazer, Yvonne N. Fondufe-Mittendorf

Research output: Contribution to journalReview articlepeer-review

9 Scopus citations

Abstract

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.

Original languageEnglish
Article numbere1617
JournalWiley Interdisciplinary Reviews: RNA
Volume12
Issue number2
DOIs
StatePublished - Mar 1 2021

Bibliographical note

Funding Information:
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.

Funding Information:
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.

Publisher Copyright:
© 2020 The Authors. WIREs RNA published by Wiley Periodicals LLC.

Keywords

  • PARP1
  • RNA biogenesis
  • chromatin
  • splicing

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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