Circadian regulation of translation.

Abstract

Most, if not all organisms exhibit robust rhythmicity of their biological functions, allowing a perpetual adaptation to external clues within the daily 24 hours-cycle. Studies on circadian rhythm regulation primarily focused on transcriptional level, considering mRNA levels to represent the primary determinant of oscillations of intracellular protein levels. However, a plethora of emerging evidence suggests that post-transcriptional regulation, particularly rhythmic mRNA translation, is not solely reliant on the oscillation of transcription. Instead, the circadian regulation of mRNA translation plays a critical role as well. A comprehensive understanding of these mechanisms underlying rhythmic translation and its regulation should bridge the gap in rhythm regulation beyond RNA fluctuations in research, and greatly enhance our comprehension of rhythm generation and maintenance. In this review, we summarize the major mechanisms of circadian regulation of translation, including regulation of translation initiation, elongation, and the alteration in rhythmic translation to external stresses, such as endoplasmic reticulum (ER) stress and ageing. We also illuminate the complex interplay between phase separation and mRNA translation. Together, we have summarized various facets of mRNA translation in circadian regulation, to set on forthcoming studies into the intricate regulatory mechanisms underpinning circadian rhythms and their implications for associated disorders.