Direct regulation of Per2 by Roraa: insights into circadian and metabolic interplay in zebrafish

Circadian rhythms are fundamental for regulating physiological processes in organisms, with disruptions often linked to metabolic disorders. This study investigated the role of the roraa gene in zebrafish, particularly its influence on circadian rhythms and metabolic regulation. Using quantitative PCR and in situ hybridization, we confirmed the rhythmic expression of roraa and explored its oscillatory mechanisms. The construction of roraa knockout mutants revealed that the absence of roraa disrupts circadian clock function, as evidenced by the reduced expression of core clock genes and altered behavioral rhythms, while the transgenic zebrafish lines which overexpress roraa just have opposite results. Additionally, we demonstrated that Roraa directly regulates per2 expression through the RORE element in its promoter. Furthermore, the transcriptome analysis and quantitative PCR indicated that the metabolism related genes, especially lipid metabolism related genes were obviously changed in roraa-/- mutants compare with WT. Our findings underscore the critical role of Roraa in coordinating circadian and metabolic processes, providing insights into potential therapeutic targets for addressing metabolic disorders related to circadian disruption.