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Tau drives translational selectivity by interacting with ribosomal proteins
There is a fundamental gap in understanding the consequences of tau–ribosome interactions. Tau oligomers and filaments hinder protein synthesis in vitro, and they associate strongly with ribosomes in vivo. Here, we investigated the consequences of tau interactions with ribosomes in transgenic mice,...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Berlin Heidelberg
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6426815/ https://www.ncbi.nlm.nih.gov/pubmed/30759285 http://dx.doi.org/10.1007/s00401-019-01970-9 |
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author | Koren, Shon A. Hamm, Matthew J. Meier, Shelby E. Weiss, Blaine E. Nation, Grant K. Chishti, Emad A. Arango, Juan Pablo Chen, Jing Zhu, Haining Blalock, Eric M. Abisambra, Jose F. |
author_facet | Koren, Shon A. Hamm, Matthew J. Meier, Shelby E. Weiss, Blaine E. Nation, Grant K. Chishti, Emad A. Arango, Juan Pablo Chen, Jing Zhu, Haining Blalock, Eric M. Abisambra, Jose F. |
author_sort | Koren, Shon A. |
collection | PubMed |
description | There is a fundamental gap in understanding the consequences of tau–ribosome interactions. Tau oligomers and filaments hinder protein synthesis in vitro, and they associate strongly with ribosomes in vivo. Here, we investigated the consequences of tau interactions with ribosomes in transgenic mice, in cells, and in human brain tissues to identify tau as a direct modulator of ribosomal selectivity. First, we performed microarrays and nascent proteomics to measure changes in protein synthesis. Using regulatable rTg4510 tau transgenic mice, we determined that tau expression differentially shifts both the transcriptome and the nascent proteome, and that the synthesis of ribosomal proteins is reversibly dependent on tau levels. We further extended these results to human brains and found that tau pathologically interacts with ribosomal protein S6 (rpS6 or S6), a crucial regulator of translation. Consequently, protein synthesis under translational control of rpS6 was reduced under tauopathic conditions in Alzheimer’s disease brains. Our data establish tau as a driver of RNA translation selectivity. Moreover, since regulation of protein synthesis is critical for learning and memory, aberrant tau–ribosome interactions in disease could explain the linkage between tauopathies and cognitive impairment. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00401-019-01970-9) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-6426815 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Springer Berlin Heidelberg |
record_format | MEDLINE/PubMed |
spelling | pubmed-64268152019-04-05 Tau drives translational selectivity by interacting with ribosomal proteins Koren, Shon A. Hamm, Matthew J. Meier, Shelby E. Weiss, Blaine E. Nation, Grant K. Chishti, Emad A. Arango, Juan Pablo Chen, Jing Zhu, Haining Blalock, Eric M. Abisambra, Jose F. Acta Neuropathol Original Paper There is a fundamental gap in understanding the consequences of tau–ribosome interactions. Tau oligomers and filaments hinder protein synthesis in vitro, and they associate strongly with ribosomes in vivo. Here, we investigated the consequences of tau interactions with ribosomes in transgenic mice, in cells, and in human brain tissues to identify tau as a direct modulator of ribosomal selectivity. First, we performed microarrays and nascent proteomics to measure changes in protein synthesis. Using regulatable rTg4510 tau transgenic mice, we determined that tau expression differentially shifts both the transcriptome and the nascent proteome, and that the synthesis of ribosomal proteins is reversibly dependent on tau levels. We further extended these results to human brains and found that tau pathologically interacts with ribosomal protein S6 (rpS6 or S6), a crucial regulator of translation. Consequently, protein synthesis under translational control of rpS6 was reduced under tauopathic conditions in Alzheimer’s disease brains. Our data establish tau as a driver of RNA translation selectivity. Moreover, since regulation of protein synthesis is critical for learning and memory, aberrant tau–ribosome interactions in disease could explain the linkage between tauopathies and cognitive impairment. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00401-019-01970-9) contains supplementary material, which is available to authorized users. Springer Berlin Heidelberg 2019-02-13 2019 /pmc/articles/PMC6426815/ /pubmed/30759285 http://dx.doi.org/10.1007/s00401-019-01970-9 Text en © The Author(s) 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. |
spellingShingle | Original Paper Koren, Shon A. Hamm, Matthew J. Meier, Shelby E. Weiss, Blaine E. Nation, Grant K. Chishti, Emad A. Arango, Juan Pablo Chen, Jing Zhu, Haining Blalock, Eric M. Abisambra, Jose F. Tau drives translational selectivity by interacting with ribosomal proteins |
title | Tau drives translational selectivity by interacting with ribosomal proteins |
title_full | Tau drives translational selectivity by interacting with ribosomal proteins |
title_fullStr | Tau drives translational selectivity by interacting with ribosomal proteins |
title_full_unstemmed | Tau drives translational selectivity by interacting with ribosomal proteins |
title_short | Tau drives translational selectivity by interacting with ribosomal proteins |
title_sort | tau drives translational selectivity by interacting with ribosomal proteins |
topic | Original Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6426815/ https://www.ncbi.nlm.nih.gov/pubmed/30759285 http://dx.doi.org/10.1007/s00401-019-01970-9 |
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