잠시만 기다려 주세요. 로딩중입니다.

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

Experimental & Molecular Medicine 2020년 52권 9호 p.22 ~ 22
Park In-Ah, 김도연, 김정아, Jang Sang-Won, 최미정, 최한경, Choe Young-Shik, 김경진,
소속 상세정보
 ( Park In-Ah ) - Daegu Gyeongbuk Institute of Science and Technology Department of Brain and Cognitive Sciences
김도연 ( Kim Do-Yeon ) - Daegu Gyeongbuk Institute of Science and Technology Department of Brain and Cognitive Sciences
김정아 ( Kim Jeong-Ah ) - Daegu Gyeongbuk Institute of Science and Technology Department of Brain and Cognitive Sciences
 ( Jang Sang-Won ) - Daegu Gyeongbuk Institute of Science and Technology Department of Brain and Cognitive Sciences
최미정 ( Choi Mi-Jung ) - Daegu Gyeongbuk Institute of Science and Technology Department of Brain and Cognitive Sciences
최한경 ( Choe Han-Kyoung ) - Daegu Gyeongbuk Institute of Science and Technology Department of Brain and Cognitive Sciences
 ( Choe Young-Shik ) - Korea Brain Research Institute Aging Neuroscience Research Group
김경진 ( Kim Kyung-Jin ) - Daegu Gyeongbuk Institute of Science and Technology Department of Brain and Cognitive Sciences

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.

키워드

Circadian rhythms; RNAi

원문 및 링크아웃 정보

등재저널 정보