Rhythmic control of AANAT translation by hnRNP Q in circadian melatonin production
Rhythmic control of AANAT translation by hnRNP Q in circadian melatonin production
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DOI：
10.1101/gad.1519507
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发表时间：
2007-04-01
影响因子：
10.5
通讯作者：
Kim, Kyong-Tai
中科院分区：
文献类型：
--
作者：
Kim, Tae-Don;Woo, Kyung-Chul;Kim, Kyong-Tai
松果体褪黑激素的昼夜节律需要血清素N-乙酰转移酶（芳基烷基胺N-乙酰转移酶[AANAT]）蛋白的夜间增加。迄今为止，只有有限的信息是可用的关键问题AANAT蛋白表达是如何上调只在夜间，无论其物种特异性的mRNA配置文件。在这里，我们表明，AANAT蛋白表达的昼夜节律的时间是由AANAT mRNA的节奏翻译调节。这种节律控制由AANAT 5'非翻译区内的高度保守的IRES（内部核糖体进入位点）元件及其伴侣hnRNP Q（异质核核糖核蛋白Q）介导，其峰值在半夜。与hnRNP Q在AANAT IRES活动中的增强作用一致，敲低hnRNP Q水平引起AANAT蛋白谱中的峰值振幅急剧下降，与松果体细胞中褪黑激素产生减少平行。AANAT mRNA的这种翻译调控为实现脊椎动物褪黑激素的昼夜节律性提供了一个新的方面。
The circadian rhythm of pineal melatonin requires the nocturnal increment of serotonin N-acetyltransferase (arylalkylamine N-acetyltransferase [AANAT]) protein. To date, only limited information is available in the critical issue of how AANAT protein expression is up-regulated exclusively at night regardless of its species-specific mRNA profiles. Here we show that the circadian timing of AANAT protein expression is regulated by rhythmic translation of AANAT mRNA. This rhythmic control is mediated by both a highly conserved IRES (internal ribosome entry site) element within the AANAT 5' untranslated region and its partner hnRNP Q (heterogeneous nuclear ribonucleoprotein Q) with a peak in the middle of the night. Consistent with the enhancing role of hnRNP Q in AANAT IRES activities, knockdown of the hnRNP Q level elicited a dramatic decrease of peak amplitude in the AANAT protein profile parallel to reduced melatonin production in pinealocytes. This translational regulation of AANAT mRNA provides a novel aspect for achieving the circadian rhythmicity of vertebrate melatonin.