Cold-induced RNA-binding proteins regulate circadian gene expression by controlling alternative polyadenylation.

Cold-induced RNA-binding proteins regulate circadian gene expression by controlling alternative polyadenylation.
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冷诱导的 RNA 结合蛋白通过控制选择性多聚腺苷酸化来调节昼夜节律基因表达

DOI:
10.1038/srep02054
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发表时间:
2013
期刊:
影响因子:
4.6
通讯作者:
Yan, Jun
Yan, Jun
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Liu, Yuting;Hu, Wenchao;Murakawa, Yasuhiro;Yin, Jingwen;Wang, Gang;Landthaler, Markus;Yan, Jun

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在哺乳动物中,体温被认为是主时钟与外围时钟同步的普遍线索,但其机制尚未完全了解。在这里,我们确定了两个冷诱导的RNA结合蛋白(RBP),Cirbp和Rbm 3,作为温度诱导的昼夜节律基因表达的重要调节因子。Cirbp或Rbm 3的缺失显著降低了核心昼夜节律基因的振幅。PAR-CLIP分析表明,Cirbp和Rbm 3的3 'UTR结合位点在多聚腺苷酸化位点(PAS)附近显着富集。此外,Cirbp和Rbm 3的缺失使3′UTR缩短,而低温(上调Cirbp和Rbm 3)使3′UTR延长。值得注意的是,我们发现它们通过与共同的3′UTR结合来抑制近端PAS的使用,并且许多由它们调节的近端/远端PAS选择的情况显示出强烈的昼夜振荡。我们的研究结果表明,Cirbp和Rbm 3通过控制交替聚腺苷酸化(阿帕)来调节昼夜节律基因的表达。
The body temperature is considered a universal cue by which the master clock synchronizes the peripheral clocks in mammals, but the mechanism is not fully understood. Here we identified two cold-induced RNA-binding proteins (RBPs), Cirbp and Rbm3, as important regulators for the temperature entrained circadian gene expression. The depletion of Cirbp or Rbm3 significantly reduced the amplitudes of core circadian genes. PAR-CLIP analyses showed that the 3′UTR binding sites of Cirbp and Rbm3 were significantly enriched near the polyadenylation sites (PASs). Furthermore, the depletion of Cirbp or Rbm3 shortened 3′UTR, whereas low temperature (upregulating Cirbp and Rbm3) lengthened 3′UTR. Remarkably, we found that they repressed the usage of proximal PASs by binding to the common 3′UTR and many cases of proximal/distal PAS selection regulated by them showed strong circadian oscillations. Our results suggested that Cirbp and Rbm3 regulated the circadian gene expression by controlling alternative polyadenylation (APA).
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