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非最佳的编码子使用会影响钟蛋白FRQ的表达,结构和功能
Mian Zhou1, Jinhu Guo, Joonseok Cha
1Department of Physiology, The University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390, USA.
Nature
|February 19, 2013
概括
在神经频率 (FRQ) 基因中,非最佳的编码子使用对于昼夜时钟功能至关重要. 优化编码子使用通过改变FRQ蛋白质结构和功能来破坏昼夜节律.
科学领域:
- 分子生物学分子生物学
- 时间生物学 时间生物学
- 遗传学 是一个遗传学.
背景情况:
- 的使用偏差通常优化高表达基因的翻译效率.
- 非最佳的编码子使用,虽然不太常见,但可能具有调节作用.
- 神经菌频率 (FRQ) 蛋白质对于生理时钟的功能至关重要.
研究的目的:
- 为了研究编码子在昼夜节律调节中的作用.
- 为了确定frq基因中非最佳的编码子使用的功能意义.
- 探索子使用如何影响FRQ蛋白质特性和昼夜时钟机制.
主要方法:
- 对frq基因与其他神经菌基因中的子使用的比较分析.
- 基因操纵是为了优化frq基因中的代使用.
- 在野生型和子优化菌株中评估昼夜节律表型 (露面和分子).
- 对FRQ蛋白水平,形状,酸化和稳定性的生物化学分析.
主要成果:
- 该frq基因在整个开放的读取框架中表现出显著的非最佳编码子使用,与大多数其他基因形成鲜明对比.
- 对于frq的Codon优化导致了公开和分子昼夜节律的完全废除.
- 在子优化后,FRQ蛋白水平增加,同时蛋白质构成,酸化和稳定性发生了意想不到的变化.
- 经过编码子优化后,在昼夜反循环中观察到FRQ功能受损.
结论:
- 对frq基因的非最佳编码子使用对于神经的昼夜钟的正常运作至关重要.
- 的使用不仅直接影响蛋白质表达水平,而且影响蛋白质的结构和功能.
- 这项研究表明了一种新的机制,即非最佳的编码子使用在生物过程中,特别是昼夜节律中,作为一个调节元件.
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