Loss of miR-83 extends lifespan and affects target gene expression in an age-dependent manner in Caenorhabditis elegans  

作　　者：Emmanuel Enoch Dzakah Ahmed Waqas Shuai Wei Bin Yu Xiaolin Wang Tao Fu Lei Liu Ge Shan 

机构地区：[1]Division of Molecular Medicine,Hefei National Laboratory for Physical Sciences at Microscale,the CAS Key Laboratory of Innate Immunity and Chronic Disease,School of Life Sciences,University of Science and Technology of China,Hefei 230027,China [2]Department of Molecular Biology and Biotechnology,School of Biological Sciences,College of Agriculture and Natural Sciences,University of Cape Coast, Cape Coast 03321,Ghana [3]CAS Centre for Excellence in Molecular Cell Science.Shanghai Institutes for Biological Sciences,Chinese Academy of Sciences,Shanghai 200031,China [4]Department of Molecular,Cellular,and Developmental Biology,University of Colorado,Boulder,Colorado 80309,USA

出　　处：《Journal of Genetics and Genomics》2018年第12期651-662,共12页遗传学报（英文版）

基　　金：supported by the CAS-TWAS President's Fellowship;supported by the National Basic Research Program of China (2015CB943000);the National Natural Science Foundation of China (3172500146 and 31471225);the Open Project of the Chinese Academy of Sciences Key Laboratory of Innate Immunity and Chronic Disease (KLIICD-201603);the Pilot Project of Hefei Centre of Materials Science and Technology (2016FXCX006);the Strategic Priority Research Program (Pilot study) "Biological basis of aging and therapeutic strategies" of the Chinese Academy of Sciences (XDPB10)

摘　　要：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.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.

关 键 词：C. elegans miR-83 daf-2 din-1 LONGEVITY 

分 类 号：R[医药卫生]