MiR-34 modulates Caenorhabditis elegans lifespan via repressing the autophagy gene atg9
MiR-34 modulates Caenorhabditis elegans lifespan via repressing the autophagy gene atg9
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DOI：
10.1007/s11357-011-9324-3
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发表时间：
2013-02-01
期刊：
影响因子：
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通讯作者：
Chen, Xiangmei
中科院分区：
文献类型：
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作者：
Yang, Jurong;Chen, Dapeng;Chen, Xiangmei
越来越多的证据表明miR-34家族在衰老过程中发挥了调节作用。然而，miR-34在体内衰老中的确切作用仍不清楚。在这里，我们报告了秀丽线虫mir-34功能丧失突变显著延缓了与年龄相关的生理衰退，延长了寿命，并增强了对高温和氧化应激的抵抗力。我们还发现，针对自噬相关基因atg4、bec-1或atg9的RNAi显著逆转了mir-34突变体的寿命延长效应。此外，miR-34a在体外转录后水平抑制Atg9A的表达，而Atg9A 3‘-UTR区的miR-34a结合序列参与了miR-34a对Atg9A表达的调控。我们的结果表明，线虫mir-34突变通过增强线虫的自噬通量来延长寿命，而miR-34通过直接抑制哺乳动物细胞中自噬相关蛋白Atg9的表达来抑制自噬。
Evidence for a regulatory role of the miR-34 family in senescence is growing. However, the exact role of miR-34 in aging in vivo remains unclear. Here, we report that a mir-34 loss-of-function mutation in Caenorhabditis elegans markedly delays the age-related physiological decline, extends lifespan, and increases resistance to heat and oxidative stress. We also found that RNAi against autophagy-related genes, atg4, bec-1, or atg9, significantly reversed the lifespan-extending effect of the mir-34 mutants. Furthermore, miR-34a inhibits Atg9A expression at the post-transcriptional level in vitro, and the miR-34a binding sequences in the 3'-UTR of Atg9A contributes to the modulation of Atg9A expression by miR-34a. Our results demonstrate that the C. elegans mir-34 mutation extends lifespan by enhancing autophagic flux in C. elegans, and that miR-34 represses autophagy by directly inhibiting the expression of the autophagy-related proteins Atg9 in mammalian cells.