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Non-optimal codon usage affects expression, structure and function of clock protein FRQ

机译:非最佳密码子使用会影响时钟蛋白FRQ的表达,结构和功能

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摘要

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.
机译:几乎在所有基因组中都观察到了密码子使用偏倚,并且认为这是由于对高效表达的基因进行高效,准确翻译的选择所致。密码子的使用也与转录,剪接和RNA结构的控制有关。许多基因显示出很少的密码子使用偏倚,这被认为反映了信使RNA翻译缺乏选择。但是,备选地,非最佳密码子使用可能具有生物学重要性。 Neurospora FREQUENCY(FRQ)蛋白的节律性表达和正常功能对于昼夜节律功能至关重要。在这里,我们表明,与Neurospora中的大多数基因不同,frq在其整个开放阅读框中都表现出非最佳密码子使用。密码子用法的优化消除了明显的和分子的昼夜节律。密码子优化不仅会增加FRQ水平,而且出乎意料的是,还会导致FRQ蛋白的构象变化,改变的FRQ磷酸化谱和稳定性,以及昼夜节律反馈回路的功能受损。这些结果表明frq的非最佳密码子使用对其昼夜节律功能至关重要。我们的研究提供了一个非最佳密码子用法如何调节蛋白质表达以及实现最佳蛋白质结构和功能的例子。

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  • 来源
    《Nature》 |2013年第7439期|111-115|共5页
  • 作者单位

    Department of Physiology, The University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390, USA;

    Department of Physiology, The University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390, USA,State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China;

    Department of Physiology, The University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390, USA;

    Department of Physiology, The University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390, USA;

    National Institute of Biological Sciences, 7 Life Science Park Road, Changping District, Beijing 102206, China;

    Departments of Neuroscience and Cell Biology and Biochemistry and Molecular Biology, The University of Texas Medical Branch, Galveston, Texas 77555-0620, USA;

    Department of Biology, Texas A&M University, College Station, Texas 77843-3258, USA;

    Department of Physiology, The University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390, USA;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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