Publication Date:
2013-02-19
Description:
Codon-usage bias has been observed in almost all genomes and is thought to result from selection for efficient and accurate translation of highly expressed genes. Codon usage is also implicated in the control of transcription, splicing and RNA structure. Many genes exhibit little codon-usage bias, which is thought to reflect a lack of selection for messenger RNA translation. Alternatively, however, non-optimal codon usage may be of biological importance. The rhythmic expression and the proper function of the Neurospora FREQUENCY (FRQ) protein are essential for circadian clock function. Here we show that, unlike most genes in Neurospora, frq exhibits non-optimal codon usage across its entire open reading frame. Optimization of frq codon usage abolishes both overt and molecular circadian rhythms. Codon optimization not only increases FRQ levels but, unexpectedly, also results in conformational changes in FRQ protein, altered FRQ phosphorylation profile and stability, and impaired functions in the circadian feedback loops. These results indicate that non-optimal codon usage of frq is essential for its circadian clock function. Our study provides an example of how non-optimal codon usage functions to regulate protein expression and to achieve optimal protein structure and function.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3629845/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3629845/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhou, Mian -- Guo, Jinhu -- Cha, Joonseok -- Chae, Michael -- Chen, She -- Barral, Jose M -- Sachs, Matthew S -- Liu, Yi -- GM062591/GM/NIGMS NIH HHS/ -- GM068496/GM/NIGMS NIH HHS/ -- GM47498/GM/NIGMS NIH HHS/ -- P01 GM068087/GM/NIGMS NIH HHS/ -- P30 AG024832/AG/NIA NIH HHS/ -- R01 GM047498/GM/NIGMS NIH HHS/ -- R01 GM062591/GM/NIGMS NIH HHS/ -- R01 GM068496/GM/NIGMS NIH HHS/ -- R01 GM084283/GM/NIGMS NIH HHS/ -- England -- Nature. 2013 Mar 7;495(7439):111-5. doi: 10.1038/nature11833. Epub 2013 Feb 17.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physiology, The University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23417067" target="_blank"〉PubMed〈/a〉
Keywords:
CLOCK Proteins/chemistry/*genetics/metabolism
;
Circadian Clocks/genetics/physiology
;
Circadian Rhythm/genetics/physiology
;
Codon/*genetics
;
Feedback, Physiological
;
Fungal Proteins/*chemistry/genetics/*metabolism
;
*Gene Expression Regulation, Fungal
;
*Neurospora crassa/chemistry/genetics/metabolism
;
Open Reading Frames
;
Phosphorylation
;
Protein Conformation
;
Protein Stability
;
Trypsin/metabolism
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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