Widespread Regulation of Translation by Elongation Pausing in Heat Shock
Global repression of protein synthesis is a hallmark of the cellular stress response and has been attributed primarily to inhibition of translation initiation, although this mechanism may not always explain the full extent of repression. Here, using ribosome footprinting, we show that 2 hr of severe...
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| Format: | Article |
| Language: | en_US |
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Elsevier B.V.
2015
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| Online Access: | http://hdl.handle.net/1721.1/96262 https://orcid.org/0000-0003-1307-882X https://orcid.org/0000-0002-7589-1798 |
| _version_ | 1826191795823837184 |
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| author | Shalgi, Reut Hurt, Jessica A. Krykbaeva, Irina Taipale, Mikko Lindquist, Susan Burge, Christopher B |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Shalgi, Reut Hurt, Jessica A. Krykbaeva, Irina Taipale, Mikko Lindquist, Susan Burge, Christopher B |
| author_sort | Shalgi, Reut |
| collection | MIT |
| description | Global repression of protein synthesis is a hallmark of the cellular stress response and has been attributed primarily to inhibition of translation initiation, although this mechanism may not always explain the full extent of repression. Here, using ribosome footprinting, we show that 2 hr of severe heat stress triggers global pausing of translation elongation at around codon 65 on most mRNAs in both mouse and human cells. The genome-wide nature of the phenomenon, its location, and features of protein N termini suggested the involvement of ribosome-associated chaperones. After severe heat shock, Hsp70’s interactions with the translational machinery were markedly altered and its association with ribosomes was reduced. Pretreatment with mild heat stress or overexpression of Hsp70 protected cells from heat shock-induced elongation pausing, while inhibition of Hsp70 activity triggered elongation pausing without heat stress. Our findings suggest that regulation of translation elongation in general, and by chaperones in particular, represents a major component of cellular stress responses. |
| first_indexed | 2024-09-23T09:01:25Z |
| format | Article |
| id | mit-1721.1/96262 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T09:01:25Z |
| publishDate | 2015 |
| publisher | Elsevier B.V. |
| record_format | dspace |
| spelling | mit-1721.1/962622022-09-30T12:52:39Z Widespread Regulation of Translation by Elongation Pausing in Heat Shock Shalgi, Reut Hurt, Jessica A. Krykbaeva, Irina Taipale, Mikko Lindquist, Susan Burge, Christopher B Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Department of Biology Whitehead Institute for Biomedical Research Shalgi, Reut Hurt, Jessica A. Krykbaeva, Irina Taipale, Mikko Lindquist, Susan Burge, Christopher B. Global repression of protein synthesis is a hallmark of the cellular stress response and has been attributed primarily to inhibition of translation initiation, although this mechanism may not always explain the full extent of repression. Here, using ribosome footprinting, we show that 2 hr of severe heat stress triggers global pausing of translation elongation at around codon 65 on most mRNAs in both mouse and human cells. The genome-wide nature of the phenomenon, its location, and features of protein N termini suggested the involvement of ribosome-associated chaperones. After severe heat shock, Hsp70’s interactions with the translational machinery were markedly altered and its association with ribosomes was reduced. Pretreatment with mild heat stress or overexpression of Hsp70 protected cells from heat shock-induced elongation pausing, while inhibition of Hsp70 activity triggered elongation pausing without heat stress. Our findings suggest that regulation of translation elongation in general, and by chaperones in particular, represents a major component of cellular stress responses. National Institute of General Medical Sciences (U.S.) (NIGMS fellowship number F32GM095060) Machiah Foundation European Molecular Biology Organization (EMBO long-term fellowship) Weitzmann Institute of Science (National Postdoctoral Award Program for Advancing Women in Science) 2015-03-30T19:23:30Z 2015-03-30T19:23:30Z 2013-02 2012-09 Article http://purl.org/eprint/type/JournalArticle 10972765 http://hdl.handle.net/1721.1/96262 Shalgi, Reut, Jessica A. Hurt, Irina Krykbaeva, Mikko Taipale, Susan Lindquist, and Christopher B. Burge. “Widespread Regulation of Translation by Elongation Pausing in Heat Shock.” Molecular Cell 49, no. 3 (February 2013): 439–452. © 2013 Elsevier Inc. https://orcid.org/0000-0003-1307-882X https://orcid.org/0000-0002-7589-1798 en_US http://dx.doi.org/10.1016/j.molcel.2012.11.028 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 B.V. Elsevier Open Archive |
| spellingShingle | Shalgi, Reut Hurt, Jessica A. Krykbaeva, Irina Taipale, Mikko Lindquist, Susan Burge, Christopher B Widespread Regulation of Translation by Elongation Pausing in Heat Shock |
| title | Widespread Regulation of Translation by Elongation Pausing in Heat Shock |
| title_full | Widespread Regulation of Translation by Elongation Pausing in Heat Shock |
| title_fullStr | Widespread Regulation of Translation by Elongation Pausing in Heat Shock |
| title_full_unstemmed | Widespread Regulation of Translation by Elongation Pausing in Heat Shock |
| title_short | Widespread Regulation of Translation by Elongation Pausing in Heat Shock |
| title_sort | widespread regulation of translation by elongation pausing in heat shock |
| url | http://hdl.handle.net/1721.1/96262 https://orcid.org/0000-0003-1307-882X https://orcid.org/0000-0002-7589-1798 |
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