Translating around the clock: Multi-level regulation of post-transcriptional processes by the circadian clock.

Abstract:

:The endogenous circadian clock functions to maintain optimal physiological health through the tissue specific coordination of gene expression and synchronization between tissues of metabolic processes throughout the 24 hour day. Individuals face numerous challenges to circadian function on a daily basis resulting in significant incidences of circadian disorders in the United States and worldwide. Dysfunction of the circadian clock has been implicated in numerous diseases including cancer, diabetes, obesity, cardiovascular and hepatic abnormalities, mood disorders and neurodegenerative diseases. The circadian clock regulates molecular, metabolic and physiological processes through rhythmic gene expression via transcriptional and post-transcriptional processes. Mounting evidence indicates that post-transcriptional regulation by the circadian clock plays a crucial role in maintaining tissue specific biological rhythms. Circadian regulation affecting RNA stability and localization through RNA processing, mRNA degradation, and RNA availability for translation can result in rhythmic protein synthesis, even when the mRNA transcripts themselves do not exhibit rhythms in abundance. The circadian clock also targets the initiation and elongation steps of translation through multiple pathways. In this review, the influence of the circadian clock across the levels of post-transcriptional, translation, and post-translational modifications are examined using examples from humans to cyanobacteria demonstrating the phylogenetic conservation of circadian regulation. Lastly, we briefly discuss chronotherapies and pharmacological treatments that target circadian function. Understanding the complexity and levels through which the circadian clock regulates molecular and physiological processes is important for future advancement of therapeutic outcomes.

journal_name

Cell Signal

journal_title

Cellular signalling

authors

Parnell AA,De Nobrega AK,Lyons LC

doi

10.1016/j.cellsig.2020.109904

subject

Has Abstract

pub_date

2020-12-25 00:00:00

pages

109904

eissn

0898-6568

issn

1873-3913

pii

S0898-6568(20)30381-8

journal_volume

80

pub_type

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