Translational contributions to tissue-specificity in rhythmic and constitutive gene expression.

BACKGROUNDThe daily gene expression oscillations that underlie mammalian circadian rhythms show striking tissue differences and involve post-transcriptional regulation. Both aspects remain poorly understood. We have used ribosome profiling to explore the contribution of translation efficiency to temporal gene expression in kidney, and contrasted our findings with liver data available from the same mice.\n\nRESULTSRhythmic translation of constantly abundant mRNAs affected largely non-overlapping transcript sets with distinct phase clustering in the two organs. Moreover, tissue differences in translation efficiency modulated the timing and amount of protein biosynthesis from rhythmic mRNAs, consistent with organ-specificity in clock output gene repertoires and rhythmicity parameters. Our comprehensive datasets provided insights into translational control beyond temporal regulation. Between tissues, many transcripts showed differences in translation efficiency, which were, however, of markedly smaller scale than mRNA abundance differences. Tissue-specific changes in translation efficiency were associated with specific transcript features and, intriguingly, globally counteracted and compensated transcript abundance variations, leading to higher similarity at the level of protein biosynthesis between both tissues.\n\nCONCLUSIONSWe show that tissue-specificity in rhythmic gene expression extends to the translatome and contributes to define the identities, the phases and the expression levels of rhythmic protein biosynthesis. Moreover, translational compensation of transcript abundance divergence leads to overall higher similarity at the level of protein production across organs. The unique resources provided through our study will serve to address fundamental questions of post-transcriptional control and differential gene expression in vivo.