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The miR-58 microRNA family is regulated by insulin signaling and contributes to lifespan regulation in Caenorhabditis elegans

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Abstract

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.

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Acknowledgements

We thank the Caenorhabditis Genetics Center (CGC), which is supported by the NIH Office of Infrastructure Programs (P40 OD010440), for providing worm strains. We also thank Dr. Li-Lin Du for critical reading of the manuscript. This work was supported by Beijing Municipal Science and Technology Commission (a fund for cultivation and development of innovation base) and the Ministry of Science and Technology of China (2014CB84980001).

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  1. College of Life Science, Beijing Normal University, Beijing, 100875, China

    Yanping Zhang

  2. National Institute of Biological Sciences, Beijing, 102206, China

    Yanping Zhang, Wenhong Zhang & Mengqiu Dong

  3. Beijing Key Laboratory of the Cell Biology of Animal Aging, Beijing, 102206, China

    Yanping Zhang, Wenhong Zhang & Mengqiu Dong

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Correspondence to Mengqiu Dong.

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Zhang, Y., Zhang, W. & Dong, M. The miR-58 microRNA family is regulated by insulin signaling and contributes to lifespan regulation in Caenorhabditis elegans. Sci. China Life Sci. 61, 1060–1070 (2018). https://doi.org/10.1007/s11427-018-9308-8

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