Liu Y, Garceau N Y, Loros J J, Dunlap J C
Department of Biochemistry, Dartmouth Medical School, Hanover, New Hampshire 03755-3844, USA.
Cell. 1997 May 2;89(3):477-86. doi: 10.1016/s0092-8674(00)80228-7.
Two forms of FRQ, a central component of the Neurospora circadian clock, arise through alternative in-frame initiation of translation. Either form alone suffices for a functional clock at some temperatures, but both are always necessary for robust rhythmicity. Temperature regulates the ratio of FRQ forms by favoring different initiation codons at different temperatures; when either initiation codon is eliminated, the temperature range permissive for rhythmicity is demonstrably reduced. This temperature-influenced choice of translation-initiation site represents a novel adaptive mechanism that extends the physiological temperature range over which clocks function. Additionally, a temperature-dependent threshold level of FRQ is required to establish the feedback loop comprising the oscillator. These data may explain how temperature limits permissive for rhythmicity are established, thus providing a molecular understanding for a basic characteristic of circadian clocks.
FRQ是粗糙脉孢菌生物钟的核心组成部分,它有两种形式,通过翻译过程中不同的框内起始方式产生。在某些温度下,任何一种形式单独存在就足以维持一个功能性的生物钟,但要实现强劲的节律性,两种形式始终都是必需的。温度通过在不同温度下偏好不同的起始密码子来调节FRQ两种形式的比例;当任何一个起始密码子被去除时,允许产生节律性的温度范围会明显缩小。这种受温度影响的翻译起始位点选择代表了一种新的适应性机制,它扩展了生物钟发挥作用的生理温度范围。此外,建立由振荡器组成的反馈回路需要一个依赖温度的FRQ阈值水平。这些数据或许可以解释允许产生节律性的温度限制是如何确立的,从而为生物钟的一个基本特征提供分子层面的理解。