coupling of a core post-translational pacemaker to a slave transcriptiontranslation feedback loop in a circadian system耦合的核心翻译后起搏器奴隶transcriptiontranslation反馈回路在生理系统.pdfVIP

Coupling of a Core Post-Translational Pacemaker to a Slave Transcription/Translation Feedback Loop in a Circadian System 1. 2. 1 1 1 Ximing Qin , Mark Byrne , Yao Xu , Tetsuya Mori , Carl Hirschie Johnson * 1 Department of Biological Sciences, Vanderbilt University, Nashville, Tennessee, United States of America, 2 Physics Department, Spring Hill College, Mobile, Alabama, United States of America Abstract Cyanobacteria are the only model circadian clock system in which a circadian oscillator can be reconstituted in vitro. The underlying circadian mechanism appears to comprise two subcomponents: a post-translational oscillator (PTO) and a transcriptional/translational feedback loop (TTFL). The PTO and TTFL have been hypothesized to operate as dual oscillator systems in cyanobacteria. However, we find that they have a definite hierarchical interdependency—the PTO is the core pacemaker while the TTFL is a slave oscillator that quickly damps when the PTO stops. By analysis of overexpression experiments and mutant clock proteins, we find that the circadian system is dependent upon the PTO and that suppression of the PTO leads to damped TTFL-based oscillations whose temperature compensation is not stable under different metabolic conditions. Mathematical modeling indicates that the experimental data are compatible with a core PTO driving the TTFL; the combined PTO/TTFL system is resilient to noise. Moreover, the modeling indicates a mechanism by which the TTFL can feed into the PTO such that new synthesis of clock proteins can phase-shift or entrain the core PTO pacemaker. This prediction was experimentally tested and confirmed by entraining the in vivo circadian system with cycles of new clock protein synthesis