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Updated: May 18, 2026
In Vitro Bioluminescence Assay to Characterize Circadian Rhythm in Mammary Epithelial Cells
Published on: September 28, 2017
Clock-controlled mir-142-3p can target its activator, Bmal1
Xiaochao Tan1, Peng Zhang, Lan Zhou
1State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Background:
microRNAs (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).
Results:
In 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.
Conclusions:
Our 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.
Insights
MicroRNAs (miRNAs) regulate the circadian clock. This study shows microRNA-142-3p directly targets BMAL1, revealing a feedback loop in core clock gene regulation.
Area of Science:
- Molecular Biology
- Genetics
- Chronobiology
Background:
- MicroRNAs (miRNAs) are implicated in circadian clock regulation.
- The specific role of miRNAs in controlling core clock genes like CLOCK and BMAL1 remains largely unelucidated.
Purpose of the Study:
- To investigate whether microRNAs can regulate the core clock genes, specifically CLOCK and BMAL1.
- To elucidate the regulatory relationship between microRNA-142-3p and BMAL1 within the circadian clock mechanism.
Main Methods:
- Utilized cell lines (293ET, NIH3T3, U87MG) for gene expression studies.
- Performed over-expression and knockdown experiments for microRNA-142-3p.
- Conducted Chromatin Immunoprecipitation (ChIP) and luciferase reporter assays to assess gene regulation.
Main Results:
- Identified microRNA-142-3p as a direct targeting molecule of the 3' untranslated region (3'UTR) of BMAL1 in both human and mouse models.
- Demonstrated that microRNA-142-3p modulates BMAL1 mRNA and protein levels, with over-expression decreasing and knockdown increasing BMAL1 expression.
- Observed oscillation of microRNA-142-3p expression in response to serum shock and confirmed direct transcriptional control by CLOCK/BMAL1 heterodimers.
Conclusions:
- Established that microRNA-142-3p directly targets BMAL1, influencing its expression levels.
- Revealed that the expression of microRNA-142-3p is regulated by CLOCK/BMAL1 heterodimers, indicating a potential negative feedback loop.
- These findings provide novel insights into the intricate molecular mechanisms governing the mammalian circadian clock.
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