Clock-controlled mir-142-3p can target its activator, Bmal1

Xiaochao Tan,Xiaozhong Peng,Lan Zhou,Peng Zhang,Hui Pan,Bin Yin

doi:10.1186/1471-2199-13-27

Abstract

BackgroundmicroRNAs (miRNAs) are shown to be involved in the regulation of circadian clock. However, it remains largely unknown whether miRNAs can regulate the core clock genes (Clock and Bmal1).ResultsIn this study, we found that mir-142-3p directly targeted the 3’UTR of human BMAL1 and mouse Bmal1. The over-expression (in 293ET and NIH3T3 cells) and knockdown (in U87MG cells) of mir-142-3p reduced and up-regulated the Bmal1/BMAL1 mRNA and protein levels, respectively. Moreover, the expression level of mir-142-3p oscillated in serum-shocked NIH3T3 cells and the results of ChIP and luciferase reporter assays suggested that the expression of mir-142-3p was directly controlled by CLOCK/BMAL1 heterodimers in NIH3T3 cells.ConclusionsOur study demonstrates that mir-142-3p can directly target the 3’UTR of Bmal1. In addition, the expression of mir-142-3p is controlled by CLOCK/BMAL1 heterodimers, suggesting a potential negative feedback loop consisting of the miRNAs and the core clock genes. These findings open new perspective for studying the molecular mechanism of circadian clock.

Highlights

MicroRNAs are shown to be involved in the regulation of circadian clock
We found that over-expression of mir-142 could significantly reduce the luciferase reporter RNA levels (Additional file 1B), suggesting that mir-142 was able to accelerate target mRNA degradation
Mir-142 expression is under clock control We have identified mir-142-3p as a potential regulator of Bmal1; it is of interest to explore the possibility that if this Bmal1-targeting miRNA is under circadian control

Summary

Introduction

MicroRNAs (miRNAs) are shown to be involved in the regulation of circadian clock. It remains largely unknown whether miRNAs can regulate the core clock genes (Clock and Bmal). The circadian clock plays important roles in local and systemic physiology and in pathology [1,2,3]. The disruption of the expression of these two core molecules leads to remarkable changes in the circadian clock. Clock knock-out mice exhibit a normal physiological rhythm because of MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate the expression of target genes at the post-transcriptional level. Kadener et al found that a miRNA, the developmental regulator bantam, plays a role in the core circadian pacemaker by targeting clock in Drosophila [15]. Mounting evidence suggests that miRNAs act as very important regulators of the circadian clock [18]

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Conclusion