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Learn MoreIntroduction: A considerable proportion of mammalian gene expression undergoes circadian oscillations. Post-transcriptional mechanisms likely make important contributions to mRNA abundance rhythms.; Aim: We have investigated how microRNAs contribute to core clock and clock-controlled gene expression using mice in which microRNA biogenesis can be inactivated in the liver.; Results: While the hepatic core clock was surprisingly resilient to microRNA loss, whole transcriptome sequencing uncovered widespread effects on clock ouput gene expression. Cyclic transcription paired with microRNA-mediated regulation was thus identified as a widespread phenomenon that affected up to 30% of the rhythmic transcriptome and served to post-transcriptionally adjust the phases and amplitudes of rhythmic mRNA accumulation. However, only a few mRNA rhythms were actually generated by microRNAs. Finally, we pinpoint several microRNAs predicted to act as modulators of rhythmic transcripts, and identify rhythmic pathways particularly prone to microRNA regulation.; Conclusion: Our study provides a comprehensive analysis of miRNA activity in shaping hepatic circadian gene expression and can serve as a valuable resource for further investigations into the regulatory roles that miRNAs play in liver gene expression and physiology. SOURCE: David Gatfield (david.gatfield@unil.ch) - University of Lausanne
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