Pluto Bioinformatics

GSE67305: Ribosome profiling reveals the rhythmic liver translatome and circadian clock regulation by upstream open reading frames

Bulk RNA sequencing

Mammalian gene expression displays widespread circadian oscillations. Rhythmic transcription underlies the core clock mechanism, but it cannot explain numerous observations made at the level of protein rhythmicity. We have used ribosome profiling in mouse liver to measure the translation of mRNAs into protein around-the-clock and at high temporal and nucleotide resolution. Transcriptome-wide, we discovered extensive rhythms in ribosome occupancy, and identified a core set of 150 mRNAs subject to particularly robust daily changes in translation efficiency. Cycling proteins produced from non-oscillating transcripts revealed thus far unknown rhythmic regulation associated with specific pathways (notably in iron metabolism, through the rhythmic translation of transcripts containing iron responsive elements, IREs), and indicated feedback to the rhythmic transcriptome through novel rhythmic transcription factors. Moreover, our data uncovered the stoichiometry in core clock protein biosynthesis and led to the identification of uORF translation as a novel mechanism regulating clock parameters such as the period length and the magnitude of gene expression oscillations. In summary, our data offer a framework for understanding the dynamics of translational regulation, circadian gene expression, and metabolic control in a solid mammalian organ. SOURCE: David Gatfield (david.gatfield@unil.ch) - University of Lausanne