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Oscillating primary transcripts harbor miRNAs with circadian functions.

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Circadian transcription of microRNAs (miRNAs) is crucial for regulating the body's internal clock. This study reveals rhythmic transcription of many miRNA primary transcripts, explaining inconsistencies in prior circadian miRNA research.

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Area of Science:

  • Molecular Biology
  • Chronobiology
  • Genetics

Background:

  • MicroRNAs (miRNAs) are key post-transcriptional regulators.
  • Their role in the circadian clock is suggested but results are inconsistent.
  • Circadian regulation impacts numerous physiological processes.

Purpose of the Study:

  • To investigate rhythmic transcription of miRNA primary transcripts in the mouse liver.
  • To understand the regulation of these transcripts by circadian factors.
  • To determine if circadian miRNA primary transcripts yield functional circadian miRNAs.

Main Methods:

  • Analysis of miRNA primary transcript transcription in mouse liver.
  • Investigated regulation by circadian transcription factors (BMAL1/CLOCK, REV-ERBα/β).
  • Over-expressed miR-378 using adenovirus and analyzed gene expression changes.

Main Results:

  • Identified at least 57 rhythmically transcribed miRNA primary transcripts in mouse liver.
  • Mature miRNAs showed weak or no oscillation, explaining prior study discrepancies.
  • Over-expression of miR-378 led to under-expression of circadian oscillating genes, including Cdkn1a and Por.
  • miR-378 modulated oscillation amplitudes of target genes in partnership with circadian transcription factors.

Conclusions:

  • Circadian transcription of miRNA primary transcripts is a significant feature of the circadian clock.
  • Rhythmic transcription of miRNA primary transcripts, not necessarily mature miRNAs, is a better indicator of circadian miRNA function.
  • This finding reconciles inconsistencies in previous circadian miRNA research and highlights a novel regulatory layer in circadian biology.