PARP1 is a versatile factor in the regulation of mRNA stability and decay

Elena A. Matveeva, Lein F. Mathbout, Yvonne N. Fondufe-Mittendorf

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

PARP1 is an abundant nuclear protein with many pleiotropic functions involved in epigenetic and transcriptional controls. Abundance of mRNA depends on the balance between synthesis and decay of a particular transcript. PARP1 binds RNA and its depletion results in increased expression of genes involved in nonsense-mediated decay, suggesting that PARP1 might be involved in mRNA stability. This is of interest considering RNA binding proteins play key roles in post-transcriptional processes in all eukaryotes. We tested the direct impact of PARP1 and PARylation on mRNA stability and decay. By measuring the half-lives of two PARP1-mRNA targets we found that the half-lives were significantly decreased in PARP1-depleted cells. PARP1 depletion impacted both the synthesis of nascent mRNA and the stability of mature mRNAs. PARylation impacted the production of nascent mRNA and the stability of mature mRNA, albeit to a lesser extent than PARP1 KD. PARylation enhanced the impact of PARP1 depletion. These studies provide the first direct comparative role of PARP1 and PARylation in RNA stability and decay, adding a new dimension as to how PARP1 regulates gene expression. These studies present a platform to begin to tease out the influence of PARP1 at each step of RNA biogenesis and decay to fine-tune gene expression.

Original languageEnglish
Article number3722
JournalScientific Reports
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2019

Bibliographical note

Funding Information:
We acknowledge the Markey Cancer Center’s Research Communications Office for manuscript editing and assistance with graphic design. This research was supported by grants from NSF MCB-1517986 (YNF-M) and NIH R01 ES024478 (YNF-M).

Publisher Copyright:
© 2019, The Author(s).

ASJC Scopus subject areas

  • General

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