Nucleic acids research · 2021
Translation elongation rate varies among organs and decreases with age.
Сравнительное исследованиеСтатьяПоддержка NIH: внешняя программаНазвание и аннотация: Перевод в очереди
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Gerashchenko Maxim V, Peterfi Zalan, Yim Sun Hee, Gladyshev Vadim N
Аннотация
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.
Предметные рубрики MeSH
AgingAnimalsCluster AnalysisCranial SinusesCycloheximideDrug Administration ScheduleHarringtoninesHigh-Throughput Nucleotide SequencingInjections, IntravenousKidneyKineticsLiverLongevityMacrolidesMaleMiceMice, Inbred C57BLMuscle, SkeletalOrbitOrgan SpecificityPeptide Chain Elongation, TranslationalPeptide Chain Initiation, TranslationalPiperidonesRibosomesTailTranscriptome