MicroRNAs shape circadian hepatic gene expression on a transcriptome-wide scale

Area of Science:

• Circadian biology
• Molecular biology
• Genetics

Background:

• A significant portion of mammalian gene expression exhibits daily circadian rhythms.
• Post-transcriptional regulation, including microRNAs (miRNAs), plays a crucial role in mRNA abundance rhythms.

Purpose of the Study:

• To investigate the contribution of microRNAs (miRNAs) to core clock and clock-controlled gene expression in the liver.
• To understand how miRNA loss affects rhythmic gene expression patterns.

Main Methods:

• Utilized genetically modified mice with inactivated hepatic miRNA biogenesis.
• Performed whole transcriptome sequencing to analyze global gene expression changes.
• bioinformatic analysis to identify rhythmic transcripts and miRNA targets.

Main Results:

• The hepatic core circadian clock showed resilience to miRNA loss.
• Widespread effects on clock output gene expression were observed, with up to 30% of the rhythmic transcriptome affected by miRNA regulation.
• miRNAs were found to post-transcriptionally adjust the phases and amplitudes of rhythmic mRNA accumulation, but rarely generated mRNA rhythms de novo.

Conclusions:

• miRNAs adapt circadian clock-driven gene expression to tissue-specific needs.
• Identified specific miRNAs that modulate rhythmic transcripts and pathways sensitive to miRNA regulation.