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PPIase dPPIL4 regulates high-amplitude PERIOD oscillations in Drosophila

ABSTRACT: Peptidyl-prolyl cis/trans isomerases (PPIases) accelerate proline peptide bond isomerization, affecting substrate protein function. In this study, through RNAi-based behavioral screening of PPIases in Drosophila melanogaster, we identified CG5808, termed Drosophila Peptidyl-Prolyl cis/trans Isomerase-like 4 (dPPIL4), as crucial for circadian rhythm regulation. Knockdown of dppil4 in clock cells lengthened the circadian rhythm period and decreased rhythmicity, accompanied by a significant reduction of core clock protein PERIOD (PER). Dppil4 knockdown downregulated per transcription and reduced phosphorylation at Ser5 in the RNA polymerase II C-terminal domain, critical for transcription elongation. In addition, dPPIL4 stabilized Cullin1 of the Skp1-Cullin1-F-box protein complex, a key regulator of PER degradation. Our findings suggest that dPPIL4 supports high-amplitude PER oscillation by enhancing both synthesis and degradation processes in a timely manner. In conclusion, our study underscores the importance of high-amplitude PER oscillations in PER for robust circadian rhythms and highlights the critical role of dPPIL4 in this process.

ORGANISM(S): Drosophila melanogaster

PROVIDER: GSE292592 | GEO | 2025/05/29

REPOSITORIES: GEO

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