Cited 3 time in webofscience Cited 3 time in scopus

microRNA-25 as a novel modulator of circadian Period2 gene oscillation

Title
microRNA-25 as a novel modulator of circadian Period2 gene oscillation
Authors
Park, InahKim, DoyeonKim, JeongahJang, SangwonChoi, MijungChoe, Han KyoungChoe, YoungshikKim, Kyungjin
DGIST Authors
Park, Inah; Kim, Doyeon; Kim, Jeongah; Jang, Sangwon; Choi, Mijung; Choe, Han Kyoung; Choe, Youngshik; Kim, Kyungjin
Issue Date
2020-09
Citation
Experimental and Molecular Medicine, 52(9), 1614-1626
Type
Article
Article Type
Article
Keywords
CIRCADIAN-CLOCKPOSTTRANSCRIPTIONAL REGULATIONPERIODTIMERHYTHMS
ISSN
1226-3613
Abstract
Circadian clock controls an organism’s biological rhythm and regulates its physiological processes in response to external time cues. Most living organisms have their own time-keeping mechanism that is maintained by transcriptional–translational autoregulatory feedback loops involving several core clock genes, such as Period. Recent studies have found the relevance between the modulation of circadian oscillation and posttranscriptional modifications by microRNAs (miRNAs). However, there are limited studies on candidate miRNAs that regulate circadian oscillation. Here, we characterize the functions of novel miRNA-25 regulating circadian Period2 (Per2) expression. Using several in silico algorithms, we identified novel miR-25-3p that, together with miR-24-3p, targets the Per2 gene. Luciferase reporter assays validated that miR-25-3p and miR-24-3p repressed Per2 expression and confirmed their predicted binding sites in the 3′-untranslated region (UTR) of Per2 mRNA. Real-time bioluminescence analyses using Per2::Luc mouse embryonic fibroblasts confirmed that PER2 protein oscillation patterns were responsive to miR-25-3p and miR-24-3. The overexpression of miR-25-3p or miR-24-3p resulted in the dampening and period shortening of the PER2::LUC oscillation, while inhibition of either miRNA increased the relative amplitude of the PER2::LUC oscillation. Notably, endogenous miR-25-3p expression in the suprachiasmatic nucleus (SCN) showed no circadian rhythmicity, but the expression levels differed in various brain regions and peripheral tissues. These results suggest that the posttranscriptional regulation of miR-25-3p and miR-24-3p may differ according to Per2 gene expression in different tissue regions. In summary, we found that novel miR-25-3p was involved in fine-tuning circadian rhythmicity by regulating Per2 oscillation at the posttranscriptional level and that it functioned synergistically with miR-24-3p to affect Per2 oscillation. © 2020, The Author(s).
URI
http://hdl.handle.net/20.500.11750/12577
DOI
10.1038/s12276-020-00496-5
Publisher
Springer Nature
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
Files:
Collection:
Department of Brain and Cognitive SciencesLaboratory of Animal Behavior and Circadian rhythm1. Journal Articles


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