文献类型：期刊文献

英文题名：Codon usage affects the structure and function of the Drosophila circadian clock protein PERIOD

作者：Fu, Jingjing[1];Murphy, Katherine A.[2];Zhou, Mian[1,3];Li, Ying H.[2];Lam, Vu H.[2];Tabuloc, Christine A.[2];Chiu, Joanna C.[2];Liu, Yi[1]

机构：[1]Univ Texas Southwestern Med Ctr Dallas, Dept Physiol, Dallas, TX 75390 USA;[2]Univ Calif Davis, Dept Entomol & Nematol, Davis, CA 95616 USA;[3]East China Univ Sci & Technol, Sch Biotechnol, Shanghai 200237, Peoples R China

年份：2016

卷号：30

期号：15

起止页码：1761

外文期刊名：GENES & DEVELOPMENT

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000382412800007)】；

基金：We thank Dr. Dong Wang, Dr. Robin Hiesinger, Dr. Huaqi Jiang, and Dr. Jin Jiang for technical assistance. We thank Dr. Adrian Rothenfluh for locomotor activity assays, and members of our laboratories for assistance. This work is supported by grants from the National Institutes of Health (R35GM118118) and the Welch Foundation (I-1560) to Y.L., and National Institutes of Health R01 GM102225 and National Science Foundation Integrative Organismal Systems 1456297 to J.C.C.

语种：英文

外文关键词：circadian clock; codon usage; Drosophila; period; protein structure

摘要：Codon usage bias is a universal feature of all genomes, but its in vivo biological functions in animal systems are not clear. To investigate the in vivo role of codon usage in animals, we took advantage of the sensitivity and robustness of the Drosophila circadian system. By codon-optimizing parts of Drosophila period (dper), a core clock gene that encodes a critical component of the circadian oscillator, we showed that dper codon usage is important for circadian clock function. Codon optimization of dper resulted in conformational changes of the dPER protein, altered dPER phosphorylation profile and stability, and impaired dPER function in the circadian negative feedback loop, which manifests into changes in molecular rhythmicity and abnormal circadian behavioral output. This study provides an in vivo example that demonstrates the role of codon usage in determining protein structure and function in an animal system. These results suggest a universal mechanism in eukaryotes that uses a codon usage "code" within genetic codons to regulate cotranslational protein folding.