Poly(ADP-Ribose) Regulates Stress Responses and MicroRNA Activity in the Cytoplasm
Author(s)Leung, Anthony; Bhutkar, Arjun (AJ); Chang, Paul; Vyas, Sejal Kamlesh; Rood, Jennifer Evelyn; Leung, Anthony; Sharp, Phillip A.; ... Show more Show less
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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.
DepartmentMassachusetts Institute of Technology. Department of Biology; MIT Program in Writing & Humanistic Studies; Koch Institute for Integrative Cancer Research at MIT
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.
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