Casein kinase 1 family regulates PRR5 and TOC1 in the Arabidopsis circadian clock

Takahiro N. Uehara, Yoshiyuki Mizutani, Keiko Kuwata, Tsuyoshi Hirota, Ayato Sato, Junya Mizoi, Saori Takao, Hiromi Matsuo, Takamasa Suzuki, Shogo Ito, Ami N. Saito, Taeko Nishiwaki-Ohkawa, Kazuko Yamaguchi-Shinozaki, Takashi Yoshimura, Steve A. Kay, Kenichiro Itami, Toshinori Kinoshita, Junichiro Yamaguchi, Norihito Nakamichi

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.