Translational switching of Cry1 protein expression confers reversible control of circadian behavior in arrhythmic Cry-deficient mice

Circadian rhythms dominate our lives through our daily cycle of sleep and wakefulness. They are controlled by a brain master clock: the suprachiasmatic nucleus (SCN). SCN timekeeping pivots around a molecular loop incorporating Cryptochrome (Cry) proteins; global loss of these proteins disables the clock. We developed a biologically appropriate translational switch based on genetic code expansion to achieve reversible control of Cry1 expression. Cry1 translation in neurons of arrhythmic Cry-null SCN slices immediately, reversibly, and dose-dependently initiated circadian molecular rhythms. Cry1 translation in SCN neurons was sufficient to initiate circadian behavior rapidly and reversibly in arrhythmic Cry-null mice. This demonstrates control of mammalian behavior using translational switching, a method of broad applicability.