Journal
NUCLEIC ACIDS RESEARCH
Volume 49, Issue 2, Pages -Publisher
OXFORD UNIV PRESS
DOI: 10.1093/nar/gkaa1103
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Funding
- NIH [DK117149, AG065403, AG047200]
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The study developed a labeling-free method to measure organ- and celltype-specific translation elongation rates, and found significant differences in elongation rates among different mouse organs. Additionally, the study revealed that the elongation rate decreases with age, indicating tight regulation of translation at the level of elongation of nascent polypeptide chains.
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 celltype-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 midlife. Thus, translation, a major metabolic process in cells, is tightly regulated at the level of elongation of nascent polypeptide chains.
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