The miRNA-192/194 cluster regulates the Period gene family and the circadian clock


R. Agami, Division of Gene Regulation, The Netherlands Cancer Institute, Plesmanlaan 121, 1066CX, Amsterdam, The Netherlands
Fax: +31(0)20 512 1999
Tel: +31(0)20 512 2079


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.