MicroRNA mir-34 provides robustness to environmental stress response via the DAF-16 network in C. elegans.
MicroRNA mir-34 provides robustness to environmental stress response via the DAF-16 network in C. elegans.
复制标题
DOI：
10.1038/srep36766
复制
发表时间：
2016-12-01
影响因子：
4.6
通讯作者：
Berezikov E
中科院分区：
文献类型：
--
作者：
Isik M;Blackwell TK;Berezikov E
不同的应激和衰老改变了microrna的表达水平，表明这些转录后调控基因表达在应激调节和长寿中起作用。早期的研究表明，miR-34家族在促进人类细胞应激后细胞周期阻滞和细胞死亡中发挥核心作用。然而，这种反应的生物学意义尚不清楚。在这里，我们表明在秀丽隐杆线虫中，mir-34的上调对于发育停滞、正确的形态发生和适应低代谢状态以保护动物免受应激相关损伤是必要的。mir-34的缺失或过表达都会导致应激反应受损，这在很大程度上可以通过DAF-16/FOXO靶基因表达的扰动来解释。我们证明mir-34的表达通过mir-34和DAF-16/FOXO之间的负反馈回路受到胰岛素信号通路的调节。我们提出mir-34通过控制DAF-16/ foxo调控基因网络中的噪声，为应激反应程序提供鲁棒性。
Diverse stresses and aging alter expression levels of microRNAs, suggesting a role for these posttranscriptional regulators of gene expression in stress modulation and longevity. Earlier studies demonstrated a central role for the miR-34 family in promoting cell cycle arrest and cell death following stress in human cells. However, the biological significance of this response was unclear. Here we show that in C. elegans mir-34 upregulation is necessary for developmental arrest, correct morphogenesis, and adaptation to a lower metabolic state to protect animals against stress-related damage. Either deletion or overexpression of mir-34 lead to an impaired stress response, which can largely be explained by perturbations in DAF-16/FOXO target gene expression. We demonstrate that mir-34 expression is regulated by the insulin signaling pathway via a negative feedback loop between miR-34 and DAF-16/FOXO. We propose that mir-34 provides robustness to stress response programs by controlling noise in the DAF-16/FOXO-regulated gene network.
登录
查看更多内容
影响因子：
64.8
作者：
Baek, Daehyun;Villen, Judit;Shin, Chanseok;Camargo, Fernando D.;Gygi, Steven P.;Bartel, David P.
通讯作者：
Bartel, David P.
影响因子：
7
作者：
Hausser J;Syed AP;Bilen B;Zavolan M
通讯作者：
Zavolan M
影响因子：
14.9
作者：
Contrino S;Smith RN;Butano D;Carr A;Hu F;Lyne R;Rutherford K;Kalderimis A;Sullivan J;Carbon S;Kephart ET;Lloyd P;Stinson EO;Washington NL;Perry MD;Ruzanov P;Zha Z;Lewis SE;Stein LD;Micklem G
通讯作者：
Micklem G
秀丽隐杆线虫中的两个保守的microRNA确保了在温度应力下的良好远端尖端细胞途径。
影响因子：
3.3
作者：
Burke SL;Hammell M;Ambros V
通讯作者：
Ambros V
影响因子：
64.8
作者：
He, Lin;He, Xingyue;Hannon, Gregory J.
通讯作者：
Hannon, Gregory J.