PARP13 regulates cellular mRNA post-transcriptionally and functions as a pro-apoptotic factor by destabilizing TRAILR4 transcript
Name
Chang_PARP13 regulates.pdf
Size
3.28 MB
Format
Adobe PDF
Checksum (MD5)
3db0b1d36b1a10198810b53936930048
Author(s)
Todorova, Tanya
Chang, Paul
Bock, Florian
Date Issued
November 2014
Journal
Nature Communications
Publisher
Nature Publishing Group
Citation
Todorova, Tanya, Florian J. Bock, and Paul Chang. “PARP13 Regulates Cellular mRNA Post-Transcriptionally and Functions as a Pro-Apoptotic Factor by Destabilizing TRAILR4 Transcript.” Nature Communications 5 (November 10, 2014): 5362.
Version
Author's final manuscript
Abstract
Poly(ADP-ribose) polymerase-13 (PARP13/ZAP/ZC3HAV1) is an antiviral factor, active against specific RNA viruses such as murine leukaemia virus, Sindbis virus and human immunodeficiency virus. During infection, PARP13 binds viral RNA via its four CCCH-type zinc-finger domains and targets it for degradation by recruiting cellular messenger RNA (mRNA) decay factors such as the exosome complex and XRN1. Here we show that PARP13 binds to and regulates cellular mRNAs in the absence of viral infection. Knockdown of PARP13 results in the misregulation of hundreds of transcripts. Among the most upregulated transcripts is TRAILR4 that encodes a decoy receptor for TRAIL—a pro-apoptotic cytokine that is a promising target for the therapeutic inhibition of cancers. PARP13 destabilizes TRAILR4 mRNA post-transcriptionally in an exosome-dependent manner by binding to a region in its 3′ untranslated region. As a consequence, PARP13 represses TRAILR4 expression and increases cell sensitivity to TRAIL-mediated apoptosis, acting as a key regulator of the cellular response to TRAIL.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Koch Institute for Integrative Cancer Research at MIT
Terms of Use
Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1038/ncomms6362
