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

BMC Mol Biol. 2012 Sep 7;13:27. doi: 10.1186/1471-2199-13-27.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • ARNTL Transcription Factors / chemistry
  • ARNTL Transcription Factors / genetics
  • ARNTL Transcription Factors / metabolism*
  • Animals
  • CLOCK Proteins / chemistry
  • CLOCK Proteins / metabolism
  • Dimerization
  • HEK293 Cells
  • Humans
  • Mice
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • NIH 3T3 Cells
  • RNA, Messenger / metabolism
  • Up-Regulation

Substances

  • 3' Untranslated Regions
  • ARNTL Transcription Factors
  • MicroRNAs
  • RNA, Messenger
  • CLOCK Proteins