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miR-83 的缺失以依赖年龄的方式延长秀丽隐杆线虫的寿命并影响靶基因的表达。

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

机构信息

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; Department of Molecular Biology and Biotechnology, School of Biological Sciences, College of Agriculture and Natural Sciences, University of Cape Coast, Cape Coast 03321, Ghana.

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.

出版信息

J Genet Genomics. 2018 Dec 20;45(12):651-662. doi: 10.1016/j.jgg.2018.11.003. Epub 2018 Dec 9.

Abstract

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.

摘要

微小 RNA(miRNA)是一种短的非编码 RNA,参与蛋白质编码基因的转录后调控。miRNA 调节多种生物的寿命和衰老过程。在这项研究中,我们鉴定了 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,而过表达 miR-83 足以降低突变体延长的寿命。我们观察到一组 miR-83 靶基因在年轻的 mir-83 突变体成虫中的表达水平上调;而在较老的 mir-83 突变体成虫中,则上调了不同的基因集。体内试验表明,miR-83 调节靶基因包括 din-1、spp-9 和 col-178 的表达,我们证明 daf-16 和 din-1 是 mir-83 突变体延长寿命所必需的。miR-83 在衰老过程中对 din-1 的调节导致了 din-1 靶基因如 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。我们鉴定了 miR-83 在调节 C. elegans 寿命中的作用,并提供了其功能机制的分子见解。

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