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Translation elongation rate varies among organs and decreases with age

There has been a surge of interest towards targeting protein synthesis to treat diseases and extend lifespan. Despite the progress, few options are available to assess translation in live animals, as their complexity limits the repertoire of experimental tools to monitor and manipulate processes wit...

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Autores principales: Gerashchenko, Maxim V, Peterfi, Zalan, Yim, Sun Hee, Gladyshev, Vadim N
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7826258/
https://www.ncbi.nlm.nih.gov/pubmed/33264395
http://dx.doi.org/10.1093/nar/gkaa1103
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author Gerashchenko, Maxim V
Peterfi, Zalan
Yim, Sun Hee
Gladyshev, Vadim N
author_facet Gerashchenko, Maxim V
Peterfi, Zalan
Yim, Sun Hee
Gladyshev, Vadim N
author_sort Gerashchenko, Maxim V
collection PubMed
description There has been a surge of interest towards targeting protein synthesis to treat diseases and extend lifespan. Despite the progress, few options are available to assess translation in live animals, as their complexity limits the repertoire of experimental tools to monitor and manipulate processes within organs and individual cells. It this study, we developed a labeling-free method for measuring organ- and cell-type-specific translation elongation rates in vivo. It is based on time-resolved delivery of translation initiation and elongation inhibitors in live animals followed by ribosome profiling. It also reports translation initiation sites in an organ-specific manner. Using this method, we found that the elongation rates differ more than 50% among mouse organs and determined them to be 6.8, 5.0 and 4.3 amino acids per second for liver, kidney, and skeletal muscle, respectively. We further found that the elongation rate is reduced by 20% between young adulthood and mid-life. Thus, translation, a major metabolic process in cells, is tightly regulated at the level of elongation of nascent polypeptide chains.
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spelling pubmed-78262582021-01-27 Translation elongation rate varies among organs and decreases with age Gerashchenko, Maxim V Peterfi, Zalan Yim, Sun Hee Gladyshev, Vadim N Nucleic Acids Res Methods Online There has been a surge of interest towards targeting protein synthesis to treat diseases and extend lifespan. Despite the progress, few options are available to assess translation in live animals, as their complexity limits the repertoire of experimental tools to monitor and manipulate processes within organs and individual cells. It this study, we developed a labeling-free method for measuring organ- and cell-type-specific translation elongation rates in vivo. It is based on time-resolved delivery of translation initiation and elongation inhibitors in live animals followed by ribosome profiling. It also reports translation initiation sites in an organ-specific manner. Using this method, we found that the elongation rates differ more than 50% among mouse organs and determined them to be 6.8, 5.0 and 4.3 amino acids per second for liver, kidney, and skeletal muscle, respectively. We further found that the elongation rate is reduced by 20% between young adulthood and mid-life. Thus, translation, a major metabolic process in cells, is tightly regulated at the level of elongation of nascent polypeptide chains. Oxford University Press 2020-12-02 /pmc/articles/PMC7826258/ /pubmed/33264395 http://dx.doi.org/10.1093/nar/gkaa1103 Text en © The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Methods Online
Gerashchenko, Maxim V
Peterfi, Zalan
Yim, Sun Hee
Gladyshev, Vadim N
Translation elongation rate varies among organs and decreases with age
title Translation elongation rate varies among organs and decreases with age
title_full Translation elongation rate varies among organs and decreases with age
title_fullStr Translation elongation rate varies among organs and decreases with age
title_full_unstemmed Translation elongation rate varies among organs and decreases with age
title_short Translation elongation rate varies among organs and decreases with age
title_sort translation elongation rate varies among organs and decreases with age
topic Methods Online
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7826258/
https://www.ncbi.nlm.nih.gov/pubmed/33264395
http://dx.doi.org/10.1093/nar/gkaa1103
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