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MicroRNAs as Modulators of Circadian gene Period2 Oscillation

MicroRNAs as Modulators of Circadian gene Period2 Oscillation
Park, InahKim, JeongahKim, DoYeonKu, Kyo JinJang, Sang WonChoi, MijungChoe, Han KyoungCheo, Young ShikKim, Kyungjin
DGIST Authors
Choe, Han Kyoung
Issue Date
The 11th UK-KOREA Neuroscience Symposium
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 auto-regulatory feedback loops (TTFLs) involving several core 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. To understand modulatory functions of miRNAs on circadian rhythm, our group have utilized one of well-established circadian gene reporter mouse line, Period2::Luciferase (PER2::LUC) knock-in mouse and selected candidate miRNAs targeting Period2 (Per2) using several in silico algorithms. Using luciferase reporter assay, this study demonstrated the regulatory effects of miR-24-3p and miR-25-3p on Per2 expression by their direct interaction with 3’ untranslated region (UTR) of Per2 mRNA. Furthermore, real-time bioluminescence analyses confirmed that PER2 protein oscillation patterns were sensitive to intracellular concentration of miR-24-3p or miR25-3p. Overexpression of either miR-24-3p or miR-25p-3p resulted in dampening and phase shortening of PER2 oscillation in miRNA concentration dependent manners, while inhibition of either miR-24-3p or miR-25-3p resulted increase in relative amplitude of PER2 oscillation in vitro. In addition, miR-24-3p or miR-25-3p overexpressing lentivirus administration to ex vivo brain slice culture of a master clock region in the hypothalamus, suprachiasmatic nucleus (SCN) also showed the dampening of PER2 oscillation, similar to in vitro results. In summary, both miR-24-3p and miR-25-3p are involved in fine-tuning of circadian rhythmicity through regulating PER2 oscillation at post-transcriptional level, and their intracellular levels are critical in modulating circadian oscillation.
Related Researcher
  • Author Choe, Han Kyoung Laboratory of Animal Behavior and Circadian rhythm
  • Research Interests Modulation of neural circuit; Circadian regulation of behavior and perception; Neurotechnology
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Department of Brain SciencesLaboratory of Animal Behavior and Circadian rhythm2. Conference Papers

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