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Cap-independent translation ensures mTOR expression and function upon protein synthesis inhibition
The mechanistic/mammalian target of rapamycin (mTOR) is a conserved serine/threonine kinase that integrates cellular signals from the nutrient and energy status to act, namely, on the protein synthesis machinery. While major advances have emerged regarding the regulators and effects of the mTOR sign...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory Press
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5648038/ https://www.ncbi.nlm.nih.gov/pubmed/28821580 http://dx.doi.org/10.1261/rna.063040.117 |
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author | Marques-Ramos, Ana Candeias, Marco M. Menezes, Juliane Lacerda, Rafaela Willcocks, Margaret Teixeira, Alexandre Locker, Nicolas Romão, Luísa |
author_facet | Marques-Ramos, Ana Candeias, Marco M. Menezes, Juliane Lacerda, Rafaela Willcocks, Margaret Teixeira, Alexandre Locker, Nicolas Romão, Luísa |
author_sort | Marques-Ramos, Ana |
collection | PubMed |
description | The mechanistic/mammalian target of rapamycin (mTOR) is a conserved serine/threonine kinase that integrates cellular signals from the nutrient and energy status to act, namely, on the protein synthesis machinery. While major advances have emerged regarding the regulators and effects of the mTOR signaling pathway, little is known about the regulation of mTOR gene expression. Here, we show that the human mTOR transcript can be translated in a cap-independent manner, and that its 5′ untranslated region (UTR) is a highly folded RNA scaffold capable of binding directly to the 40S ribosomal subunit. We further demonstrate that mTOR is able to bypass the cap requirement for translation both in normal and hypoxic conditions. Moreover, our data reveal that the cap-independent translation of mTOR is necessary for its ability to induce cell-cycle progression into S phase. These results suggest a novel regulatory mechanism for mTOR gene expression that integrates the global protein synthesis changes induced by translational inhibitory conditions. |
format | Online Article Text |
id | pubmed-5648038 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Cold Spring Harbor Laboratory Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-56480382018-11-01 Cap-independent translation ensures mTOR expression and function upon protein synthesis inhibition Marques-Ramos, Ana Candeias, Marco M. Menezes, Juliane Lacerda, Rafaela Willcocks, Margaret Teixeira, Alexandre Locker, Nicolas Romão, Luísa RNA Article The mechanistic/mammalian target of rapamycin (mTOR) is a conserved serine/threonine kinase that integrates cellular signals from the nutrient and energy status to act, namely, on the protein synthesis machinery. While major advances have emerged regarding the regulators and effects of the mTOR signaling pathway, little is known about the regulation of mTOR gene expression. Here, we show that the human mTOR transcript can be translated in a cap-independent manner, and that its 5′ untranslated region (UTR) is a highly folded RNA scaffold capable of binding directly to the 40S ribosomal subunit. We further demonstrate that mTOR is able to bypass the cap requirement for translation both in normal and hypoxic conditions. Moreover, our data reveal that the cap-independent translation of mTOR is necessary for its ability to induce cell-cycle progression into S phase. These results suggest a novel regulatory mechanism for mTOR gene expression that integrates the global protein synthesis changes induced by translational inhibitory conditions. Cold Spring Harbor Laboratory Press 2017-11 /pmc/articles/PMC5648038/ /pubmed/28821580 http://dx.doi.org/10.1261/rna.063040.117 Text en © 2017 Marques-Ramos et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed exclusively by the RNA Society for the first 12 months after the full-issue publication date (see http://rnajournal.cshlp.org/site/misc/terms.xhtml). After 12 months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/. |
spellingShingle | Article Marques-Ramos, Ana Candeias, Marco M. Menezes, Juliane Lacerda, Rafaela Willcocks, Margaret Teixeira, Alexandre Locker, Nicolas Romão, Luísa Cap-independent translation ensures mTOR expression and function upon protein synthesis inhibition |
title | Cap-independent translation ensures mTOR expression and function upon protein synthesis inhibition |
title_full | Cap-independent translation ensures mTOR expression and function upon protein synthesis inhibition |
title_fullStr | Cap-independent translation ensures mTOR expression and function upon protein synthesis inhibition |
title_full_unstemmed | Cap-independent translation ensures mTOR expression and function upon protein synthesis inhibition |
title_short | Cap-independent translation ensures mTOR expression and function upon protein synthesis inhibition |
title_sort | cap-independent translation ensures mtor expression and function upon protein synthesis inhibition |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5648038/ https://www.ncbi.nlm.nih.gov/pubmed/28821580 http://dx.doi.org/10.1261/rna.063040.117 |
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