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Loss of miR-83 extends lifespan and affects target gene expression in an age-dependent manner in Caenorhabditis elegans
- Dzakah, Emmanuel Enoch, Waqas, Ahmed, Wei, Shuai, Yu, Bin, Wang, Xiaolin, Fu, Tao, Liu, Lei, Shan, Ge
- Journal of genetics and genomics 2018 v.45 no.12 pp. 651-662
- Caenorhabditis elegans, adults, animals, gene expression regulation, gene overexpression, genes, longevity, microRNA, mutants, non-coding RNA
- 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.