title: MicroRNAs shape circadian hepatic gene expression on a transcriptome-wide scale.
abstract: A considerable proportion of mammalian gene expression undergoes circadian oscillations. Post-transcriptional mechanisms likely make important contributions to mRNA abundance rhythms. We have investigated how microRNAs (miRNAs) contribute to core clock and clock-controlled gene expression using mice in which miRNA biogenesis can be inactivated in the liver. While the hepatic core clock was surprisingly resilient to miRNA loss, whole transcriptome sequencing uncovered widespread effects on clock output gene expression. Cyclic transcription paired with miRNA-mediated regulation was thus identified as a frequent 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 few mRNA rhythms were actually generated by miRNAs. Overall, our study suggests that miRNAs function to adapt clock-driven gene expression to tissue-specific requirements. Finally, we pinpoint several miRNAs predicted to act as modulators of rhythmic transcripts, and identify rhythmic pathways particularly prone to miRNA regulation.DOI: http://dx.doi.org/10.7554/eLife.02510.001.
authors.affiliation: Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland.
authors.forename: Ngoc-Hien
authors.initials: NH
authors.lastname: Du
authors.affiliation: Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland Vital-IT, Swiss Institute of Bioinformatics, Lausanne, Switzerland.
authors.forename: Alaaddin Bulak
authors.initials: AB
authors.lastname: Arpat
authors.affiliation: Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland.
authors.forename: Mara
authors.initials: M
authors.lastname: De Matos
authors.affiliation: Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland david.gatfield@unil.ch.
authors.forename: David
authors.initials: D
authors.lastname: Gatfield
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D001683:Biological Clocks / Q000235:genetics; D015415:Biomarkers / Q000378:metabolism; D002478:Cells, Cultured; D002940:Circadian Rhythm / Q000235:genetics*; D053487:DEAD-box RNA Helicases / Q000378:metabolism; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D016678:Genome; D022781:Hepatocytes / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D056950:Period Circadian Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015203:Reproducibility of Results; D043244:Ribonuclease III / Q000378:metabolism; D017423:Sequence Analysis, RNA; D014158:Transcription, Genetic; D059467:Transcriptome / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; D015415:Biomarkers; D035683:MicroRNAs; C513312:Per2 protein, mouse; D056950:Period Circadian Proteins; D012333:RNA, Messenger; C509781:Dicer1 protein, mouse; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases
keywords: Dicer knockout; circadian clocks; liver; miRNA