miR-124/ATF-6, A Novel Lifespan Extension Pathway of Astragalus Polysaccharide in Caenorhabditis Elegans
miR-124/ATF-6, A Novel Lifespan Extension Pathway of Astragalus Polysaccharide in Caenorhabditis Elegans
复制标题
miR-124/ATF-6，一种新的黄芪多糖延长秀丽隐杆线虫寿命的途径。
DOI：
10.1002/jcb.24961
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发表时间：
2015-02-01
影响因子：
4
通讯作者：
Ai, Jing
中科院分区：
文献类型：
--
作者：
Wang, Ning;Liu, Jing;Ai, Jing
MicroRNAs (miRNAs)，尤其是进化上保守的miRNAs，在调控各种生物过程中发挥着重要作用。然而，保守的mirna在长寿中的功能在很大程度上仍然未知。黄芪多糖（Astragalus多糖，APS）最近被证实具有延长秀丽隐杆线虫寿命的作用，但其分子机制尚不完全清楚。在本研究中，我们描述了microRNA介导的秀丽隐杆线虫APS的一种新的长寿途径。我们发现APS显著延长秀丽隐杆线虫在第二和第四阶段的寿命。高度保守的miRNAmiR-124在aps处理的秀丽隐杆线虫中显著上调。过表达miR-124导致秀丽隐杆线虫的寿命延长，反之亦然，说明miR-124调控秀丽隐杆线虫的寿命。通过荧光素酶测定，我们确定atf-6是miR-124的靶基因，它作用于atf-6 30UTR的三个结合位点。一致地，agomir- cell - mir- 124也被证明可以抑制秀丽隐杆线虫中ATF-6的表达。aps处理的秀丽隐杆线虫在蛋白水平上表现出atf-6的下调。此外，通过RNAi敲低atf-6可以延长秀丽隐杆线虫的寿命，这表明miR-124调控的atf-6有助于延长寿命。综上所述，调节ATF-6的miR-124是一种新的潜在的长寿信号通路，它是线虫中APS延长寿命作用的基础。(C) 2014 Wiley期刊公司
MicroRNAs (miRNAs), especially evolutionarily conserved miRNAs play critical roles in regulating various biological process. However, the functions of conserved miRNAs in longevity are still largely unknown. Astragalus polysaccharide (APS) was recently shown to extend lifespan of Caenorhabditis elegans, but its molecular mechanisms have not been fully understood. In the present study, we characterize that microRNA mediated a novel longevity pathway of APS in C. elegans. We found that APS markedly extended the lifespan of C. elegans at the second and the fourth stages. Ahighly conserved miRNAmiR-124 was significantly upregulated inAPS-treated C. elegans. Overexpression miR-124 caused the lifespan extension of C. elegans and vice versa, indicating miR-124 regulates the longevity of C. elegans. Using luciferase assay, atf-6 was established as a target gene of miR-124 which acting on three binding sites at atf-6 30UTR. Consistently, agomir-cel-miR-124 was also shown to inhibit ATF-6 expression in C. elegans. APS-treated C. elegans showed thedown-regulation of atf-6 at protein level. Furthermore, the knockdown of atf-6 by RNAi extended the lifespan of C. elegans, indicating atf-6 regulated by miR-124 contributes to lifespan extension. Taken together, miR-124 regulating ATF-6 is a new potential longevity signal pathway, which underlies the lifespan-extending effects of APS in C. elegans. (C) 2014 Wiley Periodicals, Inc.