The miRNA-192/194 cluster regulates the Period gene family and the circadian clock.
Several biological functions in mammals are regulated in a circadian fashion. The molecular mechanisms orchestrating these circadian rhythms have been unravelled. The biological clock, with its core transcriptional unit Bmal1/CLOCK, is composed of several self-sustaining feedback loops. In this study, we describe another mechanism impinging on the core components of the circadian clock. Using a forward genetic screen, we identified the miR-192/194 cluster as a potent inhibitor of the entire Period gene family. In accordance, the exogenous expression of miR-192/194 leads to an altered circadian rhythm. Thus, our results have uncovered a new mechanism for the control of the circadian clock at the post-transcriptional level.
Nagel
Remco
R
Division of Gene Regulation, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Clijsters
Linda
L
Agami
Reuven
R
D020413:3' Untranslated Regions; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002940:Circadian Rhythm / Q000235:genetics*; D017931:DNA Primers / Q000235:genetics; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D005810:Multigene Family; D009154:Mutation; D056950:Period Circadian Proteins
D020413:3' Untranslated Regions; D017931:DNA Primers; D047908:Intracellular Signaling Peptides and Proteins; D035683:MicroRNAs; C539022:PER1 protein, human; C539023:Per1 protein, mouse; D056950:Period Circadian Proteins; D049452:Green Fluorescent Proteins