The Making and Breaking of RNAs: Dynamics of Rhythmic RNA Expression in Mammals.

The identification and characterization of rhythmically expressed mRNAs have been an active area of research over the past 20 years, as these mRNAs are believed to produce the daily rhythms in a wide range of biological processes. Circadian transcriptome studies have used mature mRNA as a primary readout and focused largely on rhythmic RNA synthesis as a regulatory mechanism underlying rhythmic mRNA expression. However, RNA synthesis, RNA degradation, or a combination of both must be rhythmic to drive rhythmic RNA profiles, and it is still unclear to what extent rhythmic synthesis leads to rhythmic RNA profiles. In addition, circadian RNA expression is also often tissue specific. Although a handful of genes cycle in all or most tissues, others are rhythmic only in certain tissues, even though the same core clock mechanism is believed to control the rhythmic RNA profiles in all tissues. This review focuses on the dynamics of rhythmic RNA synthesis and degradation and discusses how these steps collectively determine the rhythmicity, phase, and amplitude of RNA accumulation. In particular, we highlight a possible role of RNA degradation in driving tissue-specific RNA rhythms. By unifying findings from experimental and theoretical studies, we will provide a comprehensive overview of how rhythmic gene expression can be achieved and how each regulatory step contributes to tissue-specific circadian transcriptome output in mammals.