The miR-58 microRNA family is regulated by insulin signaling and contributes to lifespan regulation in Caenorhabditis elegans
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摘要:
microRNAs regulate diverse biological processes such as development and aging by promoting degradation or inhibiting translation of their target mRNAs.In this study,we have found that the miR-58 family microRNAs regulate lifespan in C.elegans.Intriguingly,members of the miR-58 family affect lifespan differently,sometimes in opposite directions,and have complex genetic interactions.The abundances of the miR-58 family miRNAs are up-regulated in the long-lived daf-2 mutant in a daf-16-dependent manner,indicating that these miRNAs are effectors of insulin signaling in C.elegans.We also found that miR-58 is regulated by insulin signaling and partially required for the lifespan extension mediated by reduced insulin signaling,germline ablation,dietary restriction,and mild mitochondrial dysfunction.We further identified the daf-21,ins-1,and isw-1 mRNAs as endogenous targets of miR-58.Our study shows that miRNAs function in multiple lifespan extension mechanisms,and that the seed sequence is not the dominant factor defining the role of a miRNA in lifespan regulation.