Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 116, Issue 23, Pages 11528-11536Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1903357116
Keywords
circadian clock; Arabidopsis; small molecule; posttranslational regulation
Categories
Funding
- Institute of Transformative Bio-Molecules research award
- Naito Foundation
- Research Program of Arid Land Research Center of Tottori University [28D2001]
- Japan Society for the Promotion of Science [17K19229, 18H02136]
- JST Precursory Research for Embryonic Science and Technology Grant [JPMJPR11B9]
- World Premier International Research Center Initiative, Japan
- Toyoake Foundation
- [16H01140]
- [15H05960]
- [15H05956]
- Grants-in-Aid for Scientific Research [17K19229, 18H02136] Funding Source: KAKEN
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The circadian clock provides organisms with the ability to adapt to daily and seasonal cycles. Eukaryotic clocks mostly rely on lineage-specific transcriptional-translational feedback loops (TTFLs). Post-translational modifications are also crucial for clock functions in fungi and animals, but the posttranslational modifications that affect the plant clock are less understood. Here, using chemical biology strategies, we show that the Arabidopsis CASEIN KINASE 1 LIKE (CKL) family is involved in posttranslational modification in the plant clock. Chemical screening demonstrated that an animal CDC7/CDK9 inhibitor, PHA767491, lengthens the Arabidopsis circadian period. Affinity proteomics using a chemical probe revealed that PHA767491 binds to and inhibits multiple CKL proteins, rather than CDC7/CDK9 homologs. Simultaneous knockdown of Arabidopsis CKL-encoding genes lengthened the circadian period. CKL4 phosphorylated transcriptional repressors PSEUDO-RESPONSE REGULA-TOR 5 (PRR5) and TIMING OF CAB EXPRESSION 1 (TOC1) in the TTFL. PHA767491 treatment resulted in accumulation of PRR5 and TOC1, accompanied by decreasing expression of PRR5- and TOC1-target genes. A prr5 toc1 double mutant was hyposensitive to PHA767491-induced period lengthening. Together, our results reveal post-translational modification of transcriptional repressors in plant clock TTFL by CK1 family proteins, which also modulate nonplant circadian clocks.
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