近日，国家生物科学研究所教授Eric Erquan Zhang及其课题组揭示了P-环NTPase RUVBL2是真核生物中保守的时钟成分。2025年3月26日出版的《自然》杂志发表了这项成果。

真核生物的生物钟通过转录-翻译反馈回路来保持时间，这一回路在包括真菌、植物和动物在内的多种生物中都呈现出一种保守的结构。尽管它们的机制相似，但这些时钟的分子组成表明它们缺乏共同的祖先。他们的研究表明，RUVBL2是一种P环NTPase酶，以前被证明作为哺乳动物时钟超级复合物的一部分影响昼夜节律的阶段和幅度，通过其非常缓慢的ATP酶活性影响昼夜节律周期，类似于蓝藻中具有良好特征的基于KaiC的时钟。RUVBL2突变体的筛选发现，在腺相关病毒传递到小鼠视交叉上核后，这些突变体的节律性、短周期和长周期改变了昼夜运动活动节律。酶促实验表明，野生型RUVBL2每天只水解大约13个ATP分子，与典型的ATP酶相比，转化率大大降低。值得注意的是，在人类、果蝇和真菌神经孢子虫中，RUVBL2同源物与核心时钟蛋白之间的物理相互作用，以及不同物种中RUVBL2突变同源物的一致昼夜节律表型，加强了它们在真核生物中的时钟相关功能。除了将RUVBL2确定为真核生物时钟的共同核心成分外，他们的研究还支持了一种观点，即最初在蓝藻中发现的慢ATP酶活性是真核生物时钟的共同特征。

附：英文原文

Title: The P-loop NTPase RUVBL2 is a conserved clock component across eukaryotes

Author: Liao, Meimei, Liu, Yanqin, Xu, Zhancong, Fang, Mingxu, Yu, Ziqing, Cui, Yufan, Sun, Zhengda, Huo, Ran, Yang, Jieyu, Huang, Fusheng, Liu, Mingming, Zhou, Qin, Song, Xiaocui, Han, Hui, Chen, She, Xu, Xiaodong, Qin, Ximing, He, Qun, Ju, Dapeng, Wang, Tao, Thakkar, Nirav, Hardin, Paul E., Golden, Susan S., Zhang, Eric Erquan

Issue&Volume: 2025-03-26

Abstract: The eukaryotic circadian clock keeps time by using a transcription–translation feedback loop, which exhibits an architecture that is conserved across a diverse range of organisms, including fungi, plants and animals1. Despite their mechanistic similarity, the molecular components of these clocks indicate a lack of common ancestry2. Our study reveals that RUVBL2, which is a P-loop NTPase enzyme previously shown to affect circadian phase and amplitude as part of mammalian clock super-complexes, influences the circadian period through its remarkably slow ATPase activity, resembling the well-characterized KaiC-based clock in cyanobacteria. A screen of RUVBL2 variants identified arrhythmic, short-period and long-period mutants that altered circadian locomotor activity rhythms following delivery by adeno-associated virus to the murine suprachiasmatic nucleus. Enzymatic assays showed that wild-type RUVBL2 hydrolyses only around 13 ATP molecules a day, a vastly reduced turnover compared with typical ATPases. Notably, physical interactions between RUVBL2 orthologues and core clock proteins in humans, Drosophila and the fungus Neurospora, along with consistent circadian phenotypes of RUVBL2-mutant orthologues across species, reinforce their clock-related function in eukaryotes. Thus, as well as establishing RUVBL2 as a common core component in eukaryotic clocks, our study supports the idea that slow ATPase activity, initially discovered in cyanobacteria, is a shared feature of eukaryotic clocks.

DOI: 10.1038/s41586-025-08797-3

Source: https://www.nature.com/articles/s41586-025-08797-3