Revealing the hidden reality of the mammalian 12-h ultradian rhythms

Biological oscillations often cycle at different harmonics of the 24-h circadian rhythms, a phenomenon we coined Musica Universalis in 2017. Like the circadian rhythm, the 12-h oscillation is also evolutionarily conserved, robust, and has recently gained new traction in the field of chronobiology. Originally thought to be regulated by the circadian clock and/or environmental cues, recent new evidences support the notion that the majority of 12-h rhythms are regulated by a distinct and cell-autonomous pacemaker that includes the unfolded protein response (UPR) transcription factor spliced form of XBP1 (XBP1s). 12-h cycle of XBP1s level in turn transcriptionally generates robust 12-h rhythms of gene expression enriched in the central dogma information flow (CEDIF) pathway. Given the regulatory and functional separation of the 12-h and circadian clocks, in this review, we will focus our attention on the mammalian 12-h pacemaker, and discuss our current understanding of its prevalence, evolutionary origin, regulation, and functional roles in both physiological and pathological processes.

Automated summary

Biological oscillations often cycle at different harmonics of the 24-hour circadian rhythms, but the 12-hour oscillation is also evolutionarily conserved and gaining attention. The 12-hour rhythms are mainly regulated by XBP1s, generating cycles of gene expression.