Robust landscapes of ribosome dwell times and aminoacyl-tRNAs in response to nutrient stress in liver
| العنوان: | Robust landscapes of ribosome dwell times and aminoacyl-tRNAs in response to nutrient stress in liver |
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| المؤلفون: | Julien Marquis, Felix Naef, Eva Martin, Nagammal Neelagandan, Frédéric Gachon, Cédric Gobet, Benjamin D. Weger |
| المصدر: | Proceedings of the National Academy of Sciences of the United States of America |
| بيانات النشر: | Proceedings of the National Academy of Sciences, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Male, Time Factors, protein synthesis, Aminoacylation, RNA, Transfer, Amino Acyl, Ribosome, Mice, 03 medical and health sciences, computational biology, Protein biosynthesis, Animals, Ribosome profiling, Amino Acids, Codon, tRNA, 030304 developmental biology, ribosome profiling, 0303 health sciences, Messenger RNA, Multidisciplinary, Chemistry, Systems Biology, 030302 biochemistry & molecular biology, Biological Sciences, Animal Feed, Mice, Inbred C57BL, A-site, Gene Expression Regulation, Liver, Biochemistry, Codon usage bias, Transfer RNA, Food Deprivation, Ribosomes |
| الوصف: | Significance Protein synthesis is a fundamental and tightly controlled process which allows organisms to respond rapidly to external signals such as nutrient availability or stress conditions. While the initiation step is well studied, the determinants of translation elongation rate on mRNAs are poorly understood, particularly in mammals. Here we combined computational and molecular biology approaches to shed light on the determinants of translation elongation rates and their relationships with aminoacyl-tRNAs in livers of normally fed and fasted mice. We found that the ribosome dwell times in mouse liver depend on codon pairs, were robust to prolonged fasting, and can be explained to some extent by a combination of aminoacyl-tRNA level and codon usage/tRNA balance. Translation depends on messenger RNA (mRNA)-specific initiation, elongation, and termination rates. While translation elongation is well studied in bacteria and yeast, less is known in higher eukaryotes. Here we combined ribosome and transfer RNA (tRNA) profiling to investigate the relations between translation elongation rates, (aminoacyl-) tRNA levels, and codon usage in mammals. We modeled codon-specific ribosome dwell times from ribosome profiling, considering codon pair interactions between ribosome sites. In mouse liver, the model revealed site- and codon-specific dwell times that differed from those in yeast, as well as pairs of adjacent codons in the P and A site that markedly slow down or speed up elongation. While translation efficiencies vary across diurnal time and feeding regimen, codon dwell times were highly stable and conserved in human. Measured tRNA levels correlated with codon usage and several tRNAs showed reduced aminoacylation, which was conserved in fasted mice. Finally, we uncovered that the longest codon dwell times could be explained by aminoacylation levels or high codon usage relative to tRNA abundance. |
| تدمد: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.1918145117 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2b8f57ce8f724fa2cd5bd482fc7968b5 https://doi.org/10.1073/pnas.1918145117 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....2b8f57ce8f724fa2cd5bd482fc7968b5 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10916490 00278424 |
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| DOI: | 10.1073/pnas.1918145117 |