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

ABSTRACT: The suprachiasmatic nucleus (SCN) is the principal circadian clock of mammals, coordinating daily rhythms of physiology and behavior. Circadian timing pivots around self-sustaining transcriptional-translational negative feedback loops (TTFLs), whereby CLOCK and BMAL1 drive the expression of the negative regulators Period and Cryptochrome (Cry). Global deletion of Cry1 and Cry2 disables the TTFL, resulting in arrhythmicity in downstream behaviors. We used this highly tractable biology to further develop genetic code expansion (GCE) as a translational switch to achieve reversible control of a biologically relevant protein, Cry1, in the SCN. This employed an orthogonal aminoacyl-tRNA synthetase/tRNA_CUA pair delivered to the SCN by adeno-associated virus (AAV) vectors, allowing inco

SUBMITTER: Maywood ES 

PROVIDER: S-EPMC6310849 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature