Regulation of Circadian Behavioral Output via a MicroRNA-JAK/STAT Circuit

Although molecular components of the circadian clock are known, mechanisms that transmit signals from the clock and produce rhythmic behavior are poorly understood. We find that the microRNA miR-279 regulates the JAK/STAT pathway to drive rest:activity rhythms in Drosophila. Overexpression of microRNA miR-279 or miR-279 deletion attenuates rest:activity rhythms. Oscillations of the clock protein PERIOD are normal in pacemaker neurons lacking miR-279, suggesting that miR-279 acts downstream of the clock. We identify the JAK/STAT ligand, Upd, as a target of miR-279 and show that knockdown of Upd rescues the behavioral phenotype of miR-279 mutants. Manipulations of the JAK/STAT pathway also disrupt circadian rhythms. In addition, central clock neurons project in the vicinity of Upd-expressing neurons, providing a possible physical connection by which the central clock could regulate JAK/STAT signaling to control rest:activity rhythms.