Codon usage affects the structure and function of the Drosophila circadian clock protein PERIOD.

Abstract:

: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.

journal_name

Genes Dev

journal_title

Genes & development

authors

Fu J,Murphy KA,Zhou M,Li YH,Lam VH,Tabuloc CA,Chiu JC,Liu Y

doi

10.1101/gad.281030.116

subject

Has Abstract

pub_date

2016-08-01 00:00:00

pages

1761-75

issue

15

eissn

0890-9369

issn

1549-5477

pii

30/15/1761

journal_volume

30

pub_type

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