James Nathan R, O'Neill John S
Division of Cell Biology, MRC Laboratory of Molecular Biology, Cambridge, UK.
Bioessays. 2025 Mar;47(3):e202300158. doi: 10.1002/bies.202300158. Epub 2024 Dec 12.
Daily rhythms in the rate and specificity of protein synthesis occur in most mammalian cells through an interaction between cell-autonomous circadian regulation and daily cycles of systemic cues. However, the overall protein content of a typical cell changes little over 24 h. For most proteins, translation appears to be coordinated with protein degradation, producing phases of proteomic renewal that maximize energy efficiency while broadly maintaining proteostasis across the solar cycle. We propose that a major function of this temporal compartmentalization-and of circadian rhythmicity in general-is to optimize the energy efficiency of protein synthesis and associated processes such as complex assembly. We further propose that much of this temporal compartmentalization is achieved at the level of translational initiation, such that the translational machinery alternates between distinct translational mechanisms, each using a distinct toolkit of phosphoproteins to preferentially recognize and translate different classes of mRNA.
大多数哺乳动物细胞中蛋白质合成的速率和特异性存在每日节律，这是通过细胞自主昼夜节律调节与全身信号的每日周期之间的相互作用实现的。然而，典型细胞的整体蛋白质含量在24小时内变化不大。对于大多数蛋白质来说，翻译似乎与蛋白质降解相协调，产生蛋白质组更新阶段，在整个太阳周期内广泛维持蛋白质稳态的同时，最大限度地提高能量效率。我们认为，这种时间分隔以及一般的昼夜节律的一个主要功能是优化蛋白质合成及相关过程（如复合物组装）的能量效率。我们进一步提出，这种时间分隔在很大程度上是在翻译起始水平实现的，这样翻译机制在不同的翻译机制之间交替，每种机制使用不同的磷酸化蛋白质工具包来优先识别和翻译不同类别的mRNA。
