MicroRNAs as modulators of circadian gene Per2 oscillation

Abstract

Circadian clock controls an organism’s biological rhythm and regulates physiological conditions in response to external time cues. Most of living organisms have their own time-keeping mechanism that is maintained by transcriptional-translational autoregulatory feedback loops involving several clock genes such as Periods, Cryptochromes, Clock and Bmal1. Recent discoveries have found the relevance between changes in circadian oscillation and post-transcriptional modification by microRNAs (miRNAs). However, the specific mechanisms of miRNAs on circadian oscillation still remain unclear. This study demonstrated the regulatory effects of miR-24-3p and miR-25-3p on Period2 (Per2) expression by direct interaction with 3’ untranslated region (UTR) of Per2 using luciferase reporter assay. Furthermore, real-time bioluminescence analyses demonstrated that PER2 oscillation patterns were sensitive to intracellular concentration of miR-24-3p or miR-25-3p. Elevation of either miR-24-3p or miR-25p-3p resulted phase advancing and dampening, while down regulation of miR-24-3p and miR-25-3p caused phase delay and increase in relative amplitude of PER2 oscillation. In summary, miR-24-3p and miR-25-3p are involved in fine-tuning of circadian rhythmicity through regulating PER2 oscillation in conjunction with other post-translational modulators. ⓒ 2017 DGIST