Circadian rhythms are nearly ubiquitous endogenous timing systems that help coordinate the myriad physiological, metabolic and developmental processes that occur continuously in each organism at all times of the day. This circadian clock is comprised at the molecular level of interlocked and autoregulatory feedback loops that are built from complex interactions that are constantly changing in relation to each throughout the 24 hour cycle. The long term goal of this project is to understand the functional relationships among the post- transcriptional processes that keep the circadian oscillator running. We are using genetic, genomic, biochemical and cell biological tools and strategies of the model plant Arabidopsis to identify the molecules and mechanisms that regulate the transport of important proteins and mRNA between the cytosol and nucleus. We are focused in part on how a range of post-translational modifications of clock proteins affect both their positional and temporal intracellular localization. Gatekeeping features of the intracellular environment will also be addressed, both on a genomic scale and at the level of a single molecular species. We are applying for the first time in circadian studies single cell imaging techniques using a photo switchable fluorescent protein to assess features of clock protein movement and turnover that will be applicable to non-plant circadian systems. We are also exploiting certain plant-specific advantages of small RNA processing to address other post- transcriptional control mechanisms of the circadian clock. Taken together our program will probe mechanisms of circadian control that should be broadly applicable across all eukaryotic systems.

Public Health Relevance

Circadian rhythms control a wide variety of processes in all eukaryotes, including linkages to the cell cycle, human metabolism and cancer. The fundamental organization of the clock as consisting of two or more, linked autoregulatory feedback loops is shared among all model systems, but the individual molecular players often vary among the kingdoms. Here post- translational mechanism of circadian clock control in Arabidopsis is investigated, with potential relevance to other eukaryotic oscillatory systems.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
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Cellular Signaling and Regulatory Systems Study Section (CSRS)
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Sesma, Michael A
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Ohio State University
Other Basic Sciences
Schools of Arts and Sciences
United States
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Jo, Hang-Hyun; Kim, Yeon Jeong; Kim, Jae Kyoung et al. (2018) Waveforms of molecular oscillations reveal circadian timekeeping mechanisms. Commun Biol 1:207
Ritter, Andrés; Iñigo, Sabrina; Fernández-Calvo, Patricia et al. (2017) The transcriptional repressor complex FRS7-FRS12 regulates flowering time and growth in Arabidopsis. Nat Commun 8:15235
Pudasaini, Ashutosh; Shim, Jae Sung; Song, Young Hun et al. (2017) Kinetics of the LOV domain of ZEITLUPE determine its circadian function in Arabidopsis. Elife 6:
Cha, Joon-Yung; Kim, Jeongsik; Kim, Tae-Sung et al. (2017) GIGANTEA is a co-chaperone which facilitates maturation of ZEITLUPE in the Arabidopsis circadian clock. Nat Commun 8:3
Choudhary, Mani K; Nomura, Yuko; Shi, Hua et al. (2016) Circadian Profiling of the Arabidopsis Proteome Using 2D-DIGE. Front Plant Sci 7:1007
Foo, Mathias; Somers, David E; Kim, Pan-Jun (2016) Kernel Architecture of the Genetic Circuitry of the Arabidopsis Circadian System. PLoS Comput Biol 12:e1004748
Choudhary, Mani Kant; Nomura, Yuko; Wang, Lei et al. (2015) Quantitative Circadian Phosphoproteomic Analysis of Arabidopsis Reveals Extensive Clock Control of Key Components in Physiological, Metabolic, and Signaling Pathways. Mol Cell Proteomics 14:2243-60
Liu, Hongtao; Wang, Qin; Liu, Yawen et al. (2013) Arabidopsis CRY2 and ZTL mediate blue-light regulation of the transcription factor CIB1 by distinct mechanisms. Proc Natl Acad Sci U S A 110:17582-7
Kim, Yumi; Lim, Junhyun; Yeom, Miji et al. (2013) ELF4 regulates GIGANTEA chromatin access through subnuclear sequestration. Cell Rep 3:671-7
Kim, Jeongsik; Geng, Ruishuang; Gallenstein, Richard A et al. (2013) The F-box protein ZEITLUPE controls stability and nucleocytoplasmic partitioning of GIGANTEA. Development 140:4060-9

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