Poly(ADP-Ribose) Regulates Stress Responses and MicroRNA Activity in the Cytoplasm
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Chang_Poly(ADP-ribose).pdf
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Author(s)
Leung, Anthony
Bhutkar, Arjun (AJ)
Chang, Paul
Vyas, Sejal Kamlesh
Rood, Jennifer Evelyn
Leung, Anthony
Sharp, Phillip A.
Date Issued
May 2011
Journal
Molecular Cell
Publisher
Elsevier
Citation
Leung, Anthony K.L., Sejal Vyas, Jennifer E. Rood, Arjun Bhutkar, Phillip A. Sharp, and Paul Chang. “Poly(ADP-Ribose) Regulates Stress Responses and MicroRNA Activity in the Cytoplasm.” Molecular Cell 42, no. 4 (May 2011): 489-499. Copyright © 2011 Elsevier Inc.
Version
Final published version
Abstract
Poly(ADP-ribose) is a major regulatory macromolecule in the nucleus, where it regulates transcription, chromosome structure, and DNA damage repair. Functions in the interphase cytoplasm are less understood. Here, we identify a requirement for poly(ADP-ribose) in the assembly of cytoplasmic stress granules, which accumulate RNA-binding proteins that regulate the translation and stability of mRNAs upon stress. We show that poly(ADP-ribose), six specific poly(ADP-ribose) polymerases, and two poly(ADP-ribose) glycohydrolase isoforms are stress granule components. A subset of stress granule proteins, including microRNA-binding Argonaute family members Ago1–4, are modified by poly(ADP-ribose), and such modification increases upon stress, a condition when both microRNA-mediated translational repression and microRNA-directed mRNA cleavage are relieved. Similar relief of repression is also observed upon overexpression of specific poly(ADP-ribose) polymerases or, conversely, upon knockdown of glycohydrolase. We conclude that poly(ADP-ribose) is a key regulator of posttranscriptional gene expression in the cytoplasm.
MIT Department
Massachusetts Institute of Technology. Department of Biology
MIT Program in Writing & Humanistic Studies
Koch Institute for Integrative Cancer Research at MIT
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DOI of Published Version
https://doi.org/10.1016/j.molcel.2011.04.015
