Molecular mechanism of temperature sensing by the circadian clock of Neurospora crassa
Molecular mechanism of temperature sensing by the circadian clock of Neurospora crassa
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DOI：
10.1101/gad.345905
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发表时间：
2005-09-01
影响因子：
10.5
通讯作者：
Brunner, M
中科院分区：
文献类型：
--
作者：
Diernfellner, ACR;Schafmeier, T;Brunner, M
脉孢菌生物钟蛋白FREQUENCY（FRQ）的长（1）和短（s）同种型的表达水平和比例对于昼夜节律的温度补偿至关重要。我们发现，1-FRQ与s-FRQ的比例是由热敏剪接内含子6的frq，一个过程中删除的翻译起始位点的1-FRQ。温度敏感性是由于在升高的温度下非共有剪接位点的识别效率低下。FRQ相对于本体蛋白的温度依赖性积累在翻译水平上受到控制。frq RNA的5 '-UTR含有六个上游开放阅读框（uORF），其处于翻译起始的非共有背景中。在uORF处扫描核糖体的热敏捕获导致主要ORF的翻译减少，并允许根据环境温度调节FRQ水平。
Expression levels and ratios of the long (1) and short (s) isoforms of the Neurospora circadian clock protein FREQUENCY (FRQ) are crucial for temperature compensation of circadian rhythms. We show that the ratio of 1-FRQ versus s-FRQ is regulated by thermosensitive splicing of intron 6 of frq, a process removing the translation initiation site of 1-FRQ. Thermosensitivity is due to inefficient recognition of nonconsensus splice sites at elevated temperature. The temperature-dependent accumulation of FRQ relative to bulk protein is controlled at the level of translation. The 5'-UTR of frq RNA contains six upstream open reading frames (uORFs) that are in nonconsensus context for translation initiation. Thermosensitive trapping of scanning ribosomes at the uORFs leads to reduced translation of the main ORF and allows adjustment of FRQ levels according to ambient temperature.