A period without PER: understanding 24-hour rhythms without classic transcription and translation feedback loops

Abstract

Since Ronald Konopka and Seymour Benzer's discovery of the gene Period in the 1970s, the circadian rhythm field has diligently investigated regulatory mechanisms and intracellular transcriptional and translation feedback loops involving Period, and these investigations culminated in a 2017 Nobel Prize in Physiology or Medicine for Michael W. Young, Michael Rosbash, and Jeffrey C. Hall. Although research on 24-hour behavior rhythms started with Period, a series of discoveries in the past decade have shown us that post-transcriptional regulation and protein modification, such as phosphorylation and oxidation, are alternatives ways to building a ticking clock.

Keywords: circadian rhythms; dopaminergic ultradian oscillator; peroxiredoxin; phosphorylation; post-transcriptional oscillator; red blood cells; transcriptional-translation feedback loop.

Figure 1.. Post-translation oscillators without transcription-translation feedback loops.

Examples of post-translation oscillators in enucleated cells such as Acetabularia and red blood cells, in unicellular alga lacking RNA rhythms, and in mice in which the classic transcription-translation feedback loop module is disrupted genetically or anatomically. KO, knockout; SCN, suprachiasmatic nucleus.