PT - JOURNAL ARTICLE AU - Violeta Castelo-Szekely AU - Alaaddin Bulak Arpat AU - Peggy Janich AU - David Gatfield TI - Translational contributions to tissue-specificity in rhythmic and constitutive gene expression AID - 10.1101/060368 DP - 2016 Jan 01 TA - bioRxiv PG - 060368 4099 - http://biorxiv.org/content/early/2016/06/23/060368.short 4100 - http://biorxiv.org/content/early/2016/06/23/060368.full AB - Gene expression oscillations constitute the molecular basis of circadian rhythms in mammalian physiology and behavior. Two molecularly poorly understood aspects of rhythmic gene expression are (1) its striking tissue-specificity and (2) the contribution of post-transcriptional mechanisms to the generation of mRNA and protein abundance oscillations. We have used ribosome profiling in mouse kidney to quantify the translation of mRNAs intro protein transcriptome-wide and around-the-clock, and we have compared the protein biosynthesis rates in this organ with those from the livers of the same cohort of animals that we reported on recently. Our analyses revealed a small set of constantly abundant transcripts in kidney (<100 genes) that underwent daily rhythms in translation. Interestingly, these translational oscillations were almost exclusively tissue-specific, as neither the identity of genes showing this phenomenon, nor the global phase distribution of translational rhythms were shared between the two organs. The analysis of the rhythmically abundant transcripts in both tissues further revealed organ specificity in the relative timing of translational vs. RNA abundance oscillations, as well as in the protein biosynthetic output of core clock genes. Finally, our transcriptome-wide data uncovered marked tissue-specificity in translation rates across constitutively expressed genes. Although in magnitude less divergent than mRNA abundances, translation efficiency was identified as an important contributor to tissue-specificity in gene expression levels. Notably, we detected a clear signature of compensation of RNA expression differences at the translational level, leading globally to higher concordance across organs at the level of ribosome footprints than of RNA abundances.