Poly(ADP-Ribose) Regulates Stress Responses and MicroRNA Activity in the Cytoplasm

Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Molecular cell (Impact Factor: 14.02). 05/2011; 42(4):489-99. DOI: 10.1016/j.molcel.2011.04.015
Source: PubMed


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.

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Available from: Anthony K. L. Leung, Apr 16, 2014
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    • "Our data support another function of the OGG1 that plays an important regulator during endotoxin-induced inflammatory response. The poly(ADPribose ) polymerase (PARP) is also a DNA repair enzyme with multifunctional activities, including chromatin remodeling, transcription, post-transcriptional gene expression, and cell death [42] [43] [44]. In addition, PARP-1 activation is associated with inflammation, indicating that targeting PARP is a valuable therapeutic strategy for inflammatory disorders, and some inhibitors are in clinical trials [45]. "
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