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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.

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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.