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首页> 外文期刊>Molecular and Cellular Biology >Circadian Amplitude of Cryptochrome 1 Is Modulated by mRNA Stability Regulation via Cytoplasmic hnRNP D Oscillation
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Circadian Amplitude of Cryptochrome 1 Is Modulated by mRNA Stability Regulation via Cytoplasmic hnRNP D Oscillation

机译：通过细胞质hnRNP D振荡的mRNA稳定性调节来调制隐色染料1的昼夜振幅。

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摘要

The mammalian circadian rhythm is observed not only at the suprachiasmatic nucleus, a master pacemaker, but also throughout the peripheral tissues. Its conserved molecular basis has been thought to consist of intracellular transcriptional feedback loops of key clock genes. However, little is known about posttranscriptional regulation of these genes. In the present study, we investigated the role of the 3′-untranslated region (3′UTR) of the mouse cryptochrome 1 (mcry1) gene at the posttranscriptional level. Mature mcry1 mRNA has a 610-nucleotide 3′UTR and mediates its own degradation. The middle part of the 3′UTR contains a destabilizing cis-acting element. The deletion of this element led to a dramatic increase in mRNA stability, and heterogeneous nuclear ribonucleoprotein D (hnRNP D) was identified as an RNA binding protein responsible for this effect. Cytoplasmic hnRNP D levels displayed a pattern that was reciprocal to the mcry1 oscillation. Knockdown of hnRNP D stabilized mcry1 mRNA and resulted in enhancement of the oscillation amplitude and a slight delay of the phase. Our results suggest that hnRNP D plays a role as a fine regulator contributing to the mcry1 mRNA turnover rate and the modulation of circadian rhythm.
机译：哺乳动物昼夜节律不仅在视交叉上核（主起搏器）处观察到，而且在整个外周组织中也观察到。人们认为它的保守分子基础由关键时钟基因的细胞内转录反馈环组成。但是，对这些基因的转录后调控了解甚少。在本研究中，我们研究了小鼠隐色1（ mcry1 ）基因在转录后水平的3'非翻译区（3'UTR）的作用。成熟的 mcry1 mRNA具有一个610个核苷酸的3'UTR，并介导其自身的降解。 3'UTR的中间部分含有一个不稳定的 cis 作用元件。该元素的缺失导致mRNA稳定性显着提高，并且异质核糖核糖核蛋白D（hnRNP D）被鉴定为是负责此作用的RNA结合蛋白。细胞质的hnRNP D水平显示出与 mcry1 振荡相对应的模式。敲低hnRNP D可稳定 mcry1 mRNA，并导致振荡幅度增强和相位稍有延迟。我们的研究结果表明，hnRNP D可以作为精细调节剂，促进 mcry1 mRNA的转化率和昼夜节律的调节。

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