Translating around the clock: Multi-level regulation of post-transcriptional processes by the circadian clock.
Translating around the clock: Multi-level regulation of post-transcriptional processes by the circadian clock.
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DOI：
10.1016/j.cellsig.2020.109904
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发表时间：
2021-04
影响因子：
4.8
通讯作者：
Lyons LC
中科院分区：
文献类型：
--
作者：
Parnell AA;De Nobrega AK;Lyons LC
内源性生物钟通过组织特异性的基因表达协调和组织间代谢和过程的同步来维持最佳的生理健康。个人每天都面临着许多昼夜节律功能的挑战，导致美国和世界各地的昼夜节律紊乱发生率很高。生物钟功能障碍与许多疾病有关，包括癌症、糖尿病、肥胖、心血管和肝脏异常、情绪障碍和神经退行性疾病。生物钟通过转录和转录后过程调控基因的节律性表达来调节分子、代谢和生理过程。越来越多的证据表明，生物钟的转录后调节在维持组织特异性生物节律中起着至关重要的作用。通过RNA加工、mRNA降解和RNA翻译可用性影响RNA稳定性和定位的昼夜节律调节可以导致有节奏的蛋白质合成，即使mRNA转录本本身并不表现出丰富的节奏。生物钟还通过多种途径靶向翻译步骤的启动和延长。在这篇综述中，跨转录后，翻译和翻译后修饰水平的生物钟的影响进行了检查，使用从人类到蓝藻的例子证明了生物钟调节的系统发育保守。最后，我们简要讨论了针对昼夜节律功能的时间疗法和药物治疗。了解生物钟调节分子和生理过程的复杂性和水平对于未来治疗结果的进步非常重要。
The endogenous circadian clock functions to maintain optimal physiological health through the tissue specific coordination of gene expression and synchronization between tissues of metabolic and 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 of 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.
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