Regulated Formation of an Amyloid-like Translational Repressor Governs Gametogenesis

Message-specific translational control is required for gametogenesis. In yeast, the RNA-binding protein Rim4 mediates translational repression of numerous mRNAs, including the B-type cyclin CLB3, which is essential for establishing the meiotic chromosome segregation pattern. Here, we show that Rim4...

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Main Authors: Berchowitz, Luke Edwin, Kabachinski, Gregory L., Walker, Margaret R., Carlile Jr, Thomas Marshal, Gilbert, Wendy, Schwartz, Thomas, Amon, Angelika B.
Other Authors: Massachusetts Institute of Technology. Department of Biology
Format: Article
Language:en_US
Published: Elsevier 2017
Online Access:http://hdl.handle.net/1721.1/107656
https://orcid.org/0000-0002-3388-7723
https://orcid.org/0000-0003-4363-441X
https://orcid.org/0000-0002-7699-9354
https://orcid.org/0000-0003-2807-9657
https://orcid.org/0000-0001-8012-1512
https://orcid.org/0000-0001-9837-0314
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author Berchowitz, Luke Edwin
Kabachinski, Gregory L.
Walker, Margaret R.
Carlile Jr, Thomas Marshal
Gilbert, Wendy
Schwartz, Thomas
Amon, Angelika B.
author2 Massachusetts Institute of Technology. Department of Biology
author_facet Massachusetts Institute of Technology. Department of Biology
Berchowitz, Luke Edwin
Kabachinski, Gregory L.
Walker, Margaret R.
Carlile Jr, Thomas Marshal
Gilbert, Wendy
Schwartz, Thomas
Amon, Angelika B.
author_sort Berchowitz, Luke Edwin
collection MIT
description Message-specific translational control is required for gametogenesis. In yeast, the RNA-binding protein Rim4 mediates translational repression of numerous mRNAs, including the B-type cyclin CLB3, which is essential for establishing the meiotic chromosome segregation pattern. Here, we show that Rim4 forms amyloid-like aggregates and that it is the amyloid-like form of Rim4 that is the active, translationally repressive form of the protein. Our data further show that Rim4 aggregation is a developmentally regulated process. Starvation induces the conversion of monomeric Rim4 into amyloid-like aggregates, thereby activating the protein to bring about repression of translation. At the onset of meiosis II, Rim4 aggregates are abruptly degraded allowing translation to commence. Although amyloids are best known for their role in the etiology of diseases such as Alzheimer’s, Parkinson’s, and diabetes by forming toxic protein aggregates, our findings show that cells can utilize amyloid-like protein aggregates to function as central regulators of gametogenesis.
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spelling mit-1721.1/1076562022-09-26T12:15:30Z Regulated Formation of an Amyloid-like Translational Repressor Governs Gametogenesis Berchowitz, Luke Edwin Kabachinski, Gregory L. Walker, Margaret R. Carlile Jr, Thomas Marshal Gilbert, Wendy Schwartz, Thomas Amon, Angelika B. Massachusetts Institute of Technology. Department of Biology Koch Institute for Integrative Cancer Research at MIT Berchowitz, Luke Edwin Kabachinski, Gregory L. Walker, Margaret R. Carlile Jr, Thomas Marshal Gilbert, Wendy Schwartz, Thomas Amon, Angelika B. Message-specific translational control is required for gametogenesis. In yeast, the RNA-binding protein Rim4 mediates translational repression of numerous mRNAs, including the B-type cyclin CLB3, which is essential for establishing the meiotic chromosome segregation pattern. Here, we show that Rim4 forms amyloid-like aggregates and that it is the amyloid-like form of Rim4 that is the active, translationally repressive form of the protein. Our data further show that Rim4 aggregation is a developmentally regulated process. Starvation induces the conversion of monomeric Rim4 into amyloid-like aggregates, thereby activating the protein to bring about repression of translation. At the onset of meiosis II, Rim4 aggregates are abruptly degraded allowing translation to commence. Although amyloids are best known for their role in the etiology of diseases such as Alzheimer’s, Parkinson’s, and diabetes by forming toxic protein aggregates, our findings show that cells can utilize amyloid-like protein aggregates to function as central regulators of gametogenesis. Charles A. King Trust (Postdoctoral Fellowship) American Cancer Society (Fellowship) National Institutes of Health (U.S.) (Grants GM62207, GM77537, and GM094303) 2017-03-22T19:50:38Z 2017-03-22T19:50:38Z 2015-09 2015-07 Article http://purl.org/eprint/type/JournalArticle 0092-8674 1097-4172 http://hdl.handle.net/1721.1/107656 Berchowitz, Luke E. et al. “Regulated Formation of an Amyloid-like Translational Repressor Governs Gametogenesis.” Cell 163.2 (2015): 406–418. https://orcid.org/0000-0002-3388-7723 https://orcid.org/0000-0003-4363-441X https://orcid.org/0000-0002-7699-9354 https://orcid.org/0000-0003-2807-9657 https://orcid.org/0000-0001-8012-1512 https://orcid.org/0000-0001-9837-0314 en_US http://dx.doi.org/10.1016/j.cell.2015.08.060 Cell Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier PMC
spellingShingle Berchowitz, Luke Edwin
Kabachinski, Gregory L.
Walker, Margaret R.
Carlile Jr, Thomas Marshal
Gilbert, Wendy
Schwartz, Thomas
Amon, Angelika B.
Regulated Formation of an Amyloid-like Translational Repressor Governs Gametogenesis
title Regulated Formation of an Amyloid-like Translational Repressor Governs Gametogenesis
title_full Regulated Formation of an Amyloid-like Translational Repressor Governs Gametogenesis
title_fullStr Regulated Formation of an Amyloid-like Translational Repressor Governs Gametogenesis
title_full_unstemmed Regulated Formation of an Amyloid-like Translational Repressor Governs Gametogenesis
title_short Regulated Formation of an Amyloid-like Translational Repressor Governs Gametogenesis
title_sort regulated formation of an amyloid like translational repressor governs gametogenesis
url http://hdl.handle.net/1721.1/107656
https://orcid.org/0000-0002-3388-7723
https://orcid.org/0000-0003-4363-441X
https://orcid.org/0000-0002-7699-9354
https://orcid.org/0000-0003-2807-9657
https://orcid.org/0000-0001-8012-1512
https://orcid.org/0000-0001-9837-0314
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