期刊
PLANT AND CELL PHYSIOLOGY
卷 63, 期 4, 页码 450-462出版社
OXFORD UNIV PRESS
DOI: 10.1093/pcp/pcac011
关键词
Arabidopsis thaliana (Arabidopsis); CDKC; 2; Chemical screening; Circadian clock; Pol II phosphorylation
资金
- Toyota Riken Scholar
- NAGASE Science Technology Foundation
- Takeda Science Foundation
- Japan Society for the Promotion of Science KAKENHI [21H05656, 18H02136, 20K21272]
- World Premier International Research Center (WPI) Initiative, Japan
- [18H04428]
- [20H05411]
- [15H05956]
- Grants-in-Aid for Scientific Research [21H05656, 20K21272, 18H02136] Funding Source: KAKEN
This study demonstrates the necessity of CDKC;2 in maintaining the circadian period in Arabidopsis. Through chemical biology and genetic approaches, it was found that CDKC;2 maintains transcriptional activity by phosphorylating the C-terminal domain of RNA polymerase II, affecting clock gene expression and period length.
The circadian clock is an internal timekeeping system that governs about 24 h biological rhythms of a broad range of developmental and metabolic activities. The clocks in eukaryotes are thought to rely on lineage-specific transcriptional-translational feedback loops. However, the mechanisms underlying the basic transcriptional regulation events for clock function have not yet been fully explored. Here, through a combination of chemical biology and genetic approaches, we demonstrate that phosphorylation of RNA polymerase II by CYCLIN DEPENDENT KINASE C; 2 (CDKC;2) is required for maintaining the circadian period in Arabidopsis. Chemical screening identified BML-259, the inhibitor of mammalian CDK2/CDK5, as a compound lengthening the circadian period of Arabidopsis. Short-term BML-259 treatment resulted in decreased expression of most clock-associated genes. Development of a chemical probe followed by affinity proteomics revealed that BML-259 binds to CDKC;2. Loss-of-function mutations of cdkc;2 caused a long period phenotype. In vitro experiments demonstrated that the CDKC;2 immunocomplex phosphorylates the C-terminal domain of RNA polymerase II, and BML-259 inhibits this phosphorylation. Collectively, this study suggests that transcriptional activity maintained by CDKC;2 is required for proper period length, which is an essential feature of the circadian clock in Arabidopsis.
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