PERfect Day: reversible and dose-dependent control of circadian time-keeping in the mouse suprachiasmatic nucleus by translational switching of PERIOD2 protein expression.

ABSTRACT: The biological clock of the suprachiasmatic nucleus (SCN) orchestrates circadian (approximately daily) rhythms of behaviour and physiology that underpin health. SCN cell-autonomous time-keeping revolves around a transcriptional/translational feedback loop (TTFL) within which PERIOD (PER1,2) and CRYPTOCHROME (CRY1,2) proteins heterodimerise and suppress trans-activation of their encoding genes (Per1,2; Cry1,2). To explore its contribution to SCN time-keeping, we used adeno-associated virus-mediated translational switching to express PER2 (tsPER2) in organotypic SCN slices carrying bioluminescent TTFL circadian reporters. Translational switching requires provision of the non-canonical amino acid, alkyne lysine (AlkK), for protein expression. Correspondingly, AlkK, but not vehicle, induced co

SUBMITTER: McManus D 

PROVIDER: S-EPMC7617102 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature