A Small-Molecule Modulator Affecting the Clock-Associated PSEUDO-RESPONSE REGULATOR 7 Amount.

This article focuses on the identification and characterization of TU-892, a novel synthetic small-molecule modulator that lengthens the circadian period in Arabidopsis thaliana by reducing the protein levels of PSEUDO-RESPONSE REGULATOR 7 (PRR7), a transcriptional repressor within the plant’s circadian transcription-translation feedback loop (TTFL). TU-892 was discovered through high-throughput screening of the Maybridge Hitfinder 10K chemical library and was shown to upregulate CIRCADIAN CLOCK–ASSOCIATED 1 (CCA1) mRNA expression by decreasing PRR7 protein stability, a process partially dependent on the PRR7 pseudo-receiver domain and proteasome activity. Unlike previously identified period-lengthening molecules that inhibit casein kinase 1–like (CKL) proteins, TU-892 does not inhibit CKL kinase activity and operates via a distinct mechanism involving PRR7 modulation. These findings suggest TU-892 as a chemical tool for studying circadian regulation and potentially for agricultural applications related to flowering time control.