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PARP13 regulates cellular mRNA post-transcriptionally and functions as a pro-apoptotic factor by destabilizing TRAILR4 transcript

Author

Listed:
  • Tanya Todorova

    (Massachusetts Institute of Technology
    Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology)

  • Florian J. Bock

    (Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology)

  • Paul Chang

    (Massachusetts Institute of Technology
    Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology)

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.

Suggested Citation

  • Tanya Todorova & Florian J. Bock & Paul Chang, 2014. "PARP13 regulates cellular mRNA post-transcriptionally and functions as a pro-apoptotic factor by destabilizing TRAILR4 transcript," Nature Communications, Nature, vol. 5(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms6362
    DOI: 10.1038/ncomms6362
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    Cited by:

    1. Shang-Jung Cheng & Temitope Gafaar & Jijin R. A. Kuttiyatveetil & Aleksandr Sverzhinsky & Carla Chen & Minghui Xu & Allison Lilley & John M. Pascal & Anthony K. L. Leung, 2025. "Regulation of stress granule maturation and dynamics by poly(ADP-ribose) interaction with PARP13," Nature Communications, Nature, vol. 16(1), pages 1-14, December.

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