Biological clocks and the coordination theory of RNA operons and regulons

One of the regulatory models of circadian rhythms involves the oscillation of transcription and translation. Although transcription factors have been widely examined during circadian processes, posttranscriptional mechanisms are less well-studied. Several laboratories have used microarrays to detect changes in mRNA expression throughout the circadian cycle and have found that mRNAs encoding the RNA-binding proteins (RBPs) nocturnin and butyrate response factor (BRF1) undergo rhythmic changes. Nocturnin is a deadenylation enzyme that removes poly(A) from the 3' ends of mRNAs, whereas BRF1 destabilizes mRNAs encoding early response gene (ERG) transcripts that contain AU-rich sequences in their 3'-untranslated regions (UTRs). Moroni and coworkers proposed that BRF1 functions as an oscillating posttranscriptional RNA operon (PTRO) that diurnally degrades ERG transcripts in peripheral organs (Keene and Tenenbaum 2002; Benjamin et al. 2006). The PTRO model posits that mRNAs can be members of one or more discrete functionally related subsets of mRNAs as determined by cis elements in mRNA and trans-acting RBPs or microRNAs that collectively recognize these cis elements (Keene 2007). This chapter describes the basis of posttranscriptional coordination by RNA operons and their potential for horizontal transfer among cells and discusses the potential for RBPs and microRNAs to participate in coordinating circadian rhythms and other biological clocks.