Rhythmic Degradation Explains and Unifies Circadian Transcriptome and Proteome Data

• The circadian clock affects both production and degradation of mRNAs and proteins
• A phase vector model explains effects of rhythmic degradation
• Rhythmic degradation causes nontrivial effects such as magnitude amplification
• Rhythmic posttranscriptional regulation affects 30% of circadian transcripts

SummaryThe rich mammalian cellular circadian output affects thousands of genes in many cell types and has been the subject of genome-wide transcriptome and proteome studies. The results have been enigmatic because transcript peak abundances do not always follow the peaks of gene-expression activity in time. We posited that circadian degradation of mRNAs and proteins plays a pivotal role in setting their peak times. To establish guiding principles, we derived a theoretical framework that fully describes the amplitudes and phases of biomolecules with circadian half-lives. We were able to explain the circadian transcriptome and proteome studies with the same unifying theory, including cases in which transcripts or proteins appeared before the onset of increased production rates. Furthermore, we estimate that 30% of the circadian transcripts in mouse liver and Drosophila heads are affected by rhythmic posttranscriptional regulation.

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