Talk abstracts
Talk on Friday 04:00-04:15pm submitted by Artem Astafev
Caloric restriction reprograms circadian rhythms in global and selective protein translation.
Artem A Astafev (Cleveland State University), Kuldeep Makwana (Cleveland State University), Josefa-Marie B. Rom, Nikkhil Velingkaar (Cleveland State University), Volha Mezhnina (Lerner Research Institute, Cleveland Clinic Foundation), Peng Jiang, Anton A Komar (Cleveland State University), Roman V Kondratov (Cleveland State University)
Abstract:
Circadian clock is a master regulator of metabolism. The anti-aging diet caloric restriction (CR) reprograms circadian transcriptome. We addressed previously overlooked factors in circadian metabolic control time resolved kinetics of protein translation in response to CR by comparing mouse liver transcriptome with translatome across the day. We found that CR affects the rhythms in global protein translation in correlation with concerted patterns in mTOR signaling and the much less studied in-vivo phosphorylation of eIF2. To study the rhythms in selective translation we have performed polysomal profiling with subsequent RNA-seq from polysomal fractions and total mRNA from mouse liver samples. Under both diets, the larger number of genes were rhythmic in polysomal fraction rather than in total RNA. We confirmed that the rhythms in expression of circadian genes and major metabolic enzymes are mainly controlled transcriptionally. We found that the cytoplasmatic and mitochondrial ribosomal proteins, as well as the components of oxidative phosphorylation chain were selectively translated in rhythmic manner with a peak specifically during the night - in synchrony with global translation rhythms on both diets. CR resulted in marked synchronization of transcriptome and translatome. Notably, CR induced robust rhythms in polysomal loading for a group of mRNAs and surprisingly, majority of them peaked predominantly during the day in antiphase with global translation rhythms suggesting selective translational control. Those mRNAs turned out to encode the proteins primarily involved in transcriptional regulation, ubiquitination reactions and stress granule dynamics.
Keywords: translation, circadian rhythms, diet