Loss of miR-83 extends lifespan and affects target gene expression in an age-dependent manner in Caenorhabditis elegans
Loss of miR-83 extends lifespan and affects target gene expression in an age-dependent manner in Caenorhabditis elegans
复制标题
miR-83 的缺失可延长秀丽隐杆线虫的寿命并以年龄依赖性方式影响靶基因表达
DOI：
10.1016/j.jgg.2018.11.003
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发表时间：
2018-12-20
影响因子：
5.9
通讯作者：
Shan, Ge
中科院分区：
文献类型：
--
作者：
Dzakah, Emmanuel Enoch;Waqas, Ahmed;Shan, Ge
microRNA（miRNAs）是一类参与蛋白质编码基因转录后调控的短链非编码RNA。miRNAs在多种生物体中调节寿命和衰老过程。在这项研究中，我们确定了miR-83在调节秀丽隐杆线虫寿命中的作用。miR-83突变体表现出延长的寿命，并且miR-83的过表达足以降低突变体的延长寿命。我们观察到一组miR-83靶基因的表达水平在年轻的mir-83突变成年人中上调;而不同的基因组在老年mir-83突变成年人中上调。体内实验表明，miR-83调节靶基因的表达，包括din-1，spp-9和col-178，我们证明了daf-16和din-1是延长mir-83突变体寿命所必需的。衰老过程中miR-83对din-1的调节导致din-1靶点如gst-4和gst-10的差异表达。在daf-2突变体中，miR-83的表达水平与野生型动物相比显著降低。我们确定了miR-83在调节C. elegans，并为其功能机制提供了分子见解。中国科学院遗传与发育生物学研究所、中国遗传学会版权所有（C）2018由Elsevier Limited和Science Press出版。All rights reserved.
MicroRNAs (miRNAs) are short non-coding RNAs that are involved in the post-transcriptional regulation of protein-coding genes. miRNAs modulate lifespan and the aging process in a variety of organisms. In this study, we identified a role of miR-83 in regulating lifespan of Caenorhabditis elegans. mir-83 mutants exhibited extended lifespan, and the overexpression of miR-83 was sufficient to decrease the prolonged lifespan of the mutants. We observed upregulation of the expression levels of a set of miR-83 target genes in young mir-83 mutant adults; while different sets of genes were upregulated in older mir-83 mutant adults. In vivo assays showed that miR-83 regulated expression of target genes including din-1, spp-9 and col-178, and we demonstrated that daf-16 and din-1 were required for the extension of lifespan in the mir-83 mutants. The regulation of din-1 by miR-83 during aging resulted in the differential expression of din-1 targets such as gst-4 and gst-10. In daf-2 mutants, the expression level of miR-83 was significantly reduced compared to wild-type animals. We identified a role for miR-83 in modulating lifespan in C. elegans and provided molecular insights into its functional mechanism. Copyright (C) 2018, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, and Genetics Society of China. Published by Elsevier Limited and Science Press. All rights reserved.