Cap-independent translation ensures mTOR expression and function upon protein synthesis inhibition
| Autor: | Rafaela Lacerda, Margaret M. Willcocks, Nicolas Locker, Juliane Menezes, Alexandre Teixeira, Luísa Romão, Ana Marques-Ramos, Marco M. Candeias |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Untranslated region RNA Caps RNA Folding Biology mTORC2 Article Cell Line Evolution Molecular 03 medical and health sciences Eukaryotic translation Luciferases Firefly Gene expression Protein biosynthesis Animals Humans RNA Messenger Molecular Biology PI3K/AKT/mTOR pathway Protein Synthesis Inhibitors 030102 biochemistry & molecular biology TOR Serine-Threonine Kinases Hydrazones Translation (biology) HCT116 Cells Cell Hypoxia Cell biology Internal ribosome entry site Thiazoles 030104 developmental biology HEK293 Cells Gene Expression Regulation Protein Biosynthesis S Phase Cell Cycle Checkpoints 5' Untranslated Regions HeLa Cells |
| Zdroj: | RNA (New York, N.Y.). 23(11) |
| ISSN: | 1469-9001 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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