Poly(ADP-Ribose) Regulates Stress Responses and MicroRNA Activity in the Cytoplasm
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 gr...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | en_US |
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Elsevier
2014
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| Online Access: | http://hdl.handle.net/1721.1/84591 https://orcid.org/0000-0003-1465-1691 |
| _version_ | 1826189603581722624 |
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| author | Leung, Anthony Bhutkar, Arjun (AJ) Chang, Paul Vyas, Sejal Kamlesh Rood, Jennifer Evelyn Leung, Anthony Sharp, Phillip A. |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Leung, Anthony Bhutkar, Arjun (AJ) Chang, Paul Vyas, Sejal Kamlesh Rood, Jennifer Evelyn Leung, Anthony Sharp, Phillip A. |
| author_sort | Leung, Anthony |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T08:18:35Z |
| format | Article |
| id | mit-1721.1/84591 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T08:18:35Z |
| publishDate | 2014 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/845912022-09-30T08:54:16Z Poly(ADP-Ribose) Regulates Stress Responses and MicroRNA Activity in the Cytoplasm Leung, Anthony Bhutkar, Arjun (AJ) Chang, Paul Vyas, Sejal Kamlesh Rood, Jennifer Evelyn Leung, Anthony Sharp, Phillip A. Massachusetts Institute of Technology. Department of Biology MIT Program in Writing & Humanistic Studies Koch Institute for Integrative Cancer Research at MIT Leung, Anthony K.L. Vyas, Sejal Kamlesh Rood, Jennifer Evelyn Bhutkar, Arjun (AJ) Sharp, Phillip A. Chang, Paul 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. National Institutes of Health (U.S.) (Grant RO1-CA133404) National Cancer Institute (U.S.) (Grant PO1-CA42063) National Cancer Institute (U.S.) (Cancer Center Support Core Grant P30-CA14051) 2014-01-27T18:31:08Z 2014-01-27T18:31:08Z 2011-05 2011-03 Article http://purl.org/eprint/type/JournalArticle 10972765 1097-4164 http://hdl.handle.net/1721.1/84591 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. https://orcid.org/0000-0003-1465-1691 en_US http://dx.doi.org/10.1016/j.molcel.2011.04.015 Molecular Cell 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. application/pdf Elsevier Elsevier Open Archive |
| spellingShingle | Leung, Anthony Bhutkar, Arjun (AJ) Chang, Paul Vyas, Sejal Kamlesh Rood, Jennifer Evelyn Leung, Anthony Sharp, Phillip A. Poly(ADP-Ribose) Regulates Stress Responses and MicroRNA Activity in the Cytoplasm |
| title | Poly(ADP-Ribose) Regulates Stress Responses and MicroRNA Activity in the Cytoplasm |
| title_full | Poly(ADP-Ribose) Regulates Stress Responses and MicroRNA Activity in the Cytoplasm |
| title_fullStr | Poly(ADP-Ribose) Regulates Stress Responses and MicroRNA Activity in the Cytoplasm |
| title_full_unstemmed | Poly(ADP-Ribose) Regulates Stress Responses and MicroRNA Activity in the Cytoplasm |
| title_short | Poly(ADP-Ribose) Regulates Stress Responses and MicroRNA Activity in the Cytoplasm |
| title_sort | poly adp ribose regulates stress responses and microrna activity in the cytoplasm |
| url | http://hdl.handle.net/1721.1/84591 https://orcid.org/0000-0003-1465-1691 |
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