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miR‐124/ATF‐6, A Novel Lifespan Extension Pathway of Astragalus Polysaccharide in Caenorhabditis Elegans
Author(s) -
Wang Ning,
Liu Jing,
Xie Fang,
Gao Xu,
Ye JianHan,
Sun LuYao,
Wei Ran,
Ai Jing
Publication year - 2015
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.24961
Subject(s) - caenorhabditis elegans , biology , rna interference , gene knockdown , longevity , microrna , microbiology and biotechnology , caenorhabditis , model organism , genetics , gene , rna
MicroRNAs (miRNAs), especially evolutionarily conserved miRNAs play critical roles in regulating various biological process. However, the functions of conserved miRNAs in longevity are still largely unknown. Astragalus polysaccharide (APS) was recently shown to extend lifespan of Caenorhabditis elegans , but its molecular mechanisms have not been fully understood. In the present study, we characterize that microRNA mediated a novel longevity pathway of APS in C. elegans . We found that APS markedly extended the lifespan of C. elegans at the second and the fourth stages. A highly conserved miRNA miR‐124 was significantly upregulated in APS‐treated C. elegans . Overexpression miR‐124 caused the lifespan extension of C. elegans and vice versa, indicating miR‐124 regulates the longevity of C. elegans . Using luciferase assay, atf‐6 was established as a target gene of miR‐124 which acting on three binding sites at atf‐6 3′UTR. Consistently, agomir‐ cel‐miR‐124 was also shown to inhibit ATF‐6 expression in C. elegans . APS‐treated C. elegans showed the down‐regulation of atf‐6 at protein level. Furthermore, the knockdown of atf‐6 by RNAi extended the lifespan of C. elegans , indicating atf‐6 regulated by miR‐124 contributes to lifespan extension. Taken together, miR‐124 regulating ATF‐6 is a new potential longevity signal pathway, which underlies the lifespan‐extending effects of APS in C. elegans . J. Cell. Biochem. 116: 242–251, 2015. © 2014 Wiley Periodicals, Inc.