Communications in Information and Systems

Volume 22 (2022)

Number 3

Special issue on bioinformatics and biophysics in honor of professor Michael Waterman on his 80th birthday

Guest Editors: Fengzhu Sun (University of Southern California), Guowei Wei (Michigan State University), Stephen S.-T. Yau (Tsinghua University), and Shan Zhao (University of Alabama)

Dissecting role of AAA-ATPase RUVBLs in circadian system via mathematical modeling

Pages: 401 – 427

DOI: https://dx.doi.org/10.4310/CIS.2022.v22.n3.a6

Authors

Ziqing Yu (National Institute of Biological Sciences, Beijing, China; and Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China)

Erquan Zhang (National Institute of Biological Sciences, Beijing, China; and Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China)

Abstract

The circadian genes in mammals are involved in a transcriptiontranslation feedback loop, whereas in cyanobacteria, there exists a post-translational oscillator (PTO) consisting of KaiA, KaiB, and KaiC. KaiC has both ATPase and kinase activities. ATP binding, hydrolysis and phosphate transfer drive the dynamics of circadian system. In this study, we built a mathematical model for our latest found circadian genes Ruvbl1/2 (Ruvbls) and added the model to a previously published model for mammalian circadian system. RUVBLs are the first ATPase known to directly participate in the mammalian circadian system. We described the entire process whereby an ATPase is involved in the traditional transcriptiontranslation feedback loop. Additionally, a phase-shift adenosinelike molecule, cordycepin, which was discovered from our highthroughput screening and targeted RUVBLs, was also simulated in our mathematical model. Notably, this model gives a more detailed description of circadian system, and considers the participation of ATPase for the first time, which can lead to a deeper insight into mammalian circadian clock regulation. Our model aligns well our experimental data. Further, based on wet-lab experiments and drylab modeling, we discussed the role of ATP and ATPase in mammalian circadian system. Finally, we compared the similarities and differences between KaiC and RUVBLs, and discussed the potential of RUVBLs as a component of mammalian post-translational oscillator.

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The authors’ research was supported by the funds from MOST of China (2021ZD0203400) and NSFC (31971090).

Received 14 January 2022

Published 22 July 2022