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Caenorhabditis elegans eyes absent ortholog EYA-1 Is required for stress resistance

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Abstract

Eyes absent (Eya) is a highly conserved transcription cofactor and protein phosphatase that regulates multiple developmental processes throughout the metazoans. It is a dual function protein, working as a transcription factor in the nucleus and as a tyrosine phosphatase in the cytoplasm. In this study, we isolated EYA-1 of Caenorhabditis elegans, the only homolog of Eyes absent, and set up an effective feeding-based RNAi (RNA interference) against the gene. We found that knockdown of EYA-1 decreased heat and oxidative stress tolerance and accelerated the onset of paralysis mediated by Aβ1-42 proteotoxicity and polyQ. Under heat stress (35°C), EYA-1 knockdown shortened the mean lifespan by 16.8%, which could be attributed to decrease in heat shock protein-16.2 (hsp-16.2) expression. Under oxidative stress, EYA-1 knockdown could shorten the mean lifespan by 18.7%, which could be attributed to intracellular ROS accumulation and the decrease of superoxide dismutase-3 (sod-3) protein expression. Moreover, EYA-1 knockdown animals also showed increased lipofuscin accumulation under oxidative stress. Further studies demonstrated that EYA-1 knockdown could not inhibit daf-16 nuclear accumulation in wild-type worms in response to stress. On the other hand, EYA-1 deficiency did not further reduce stress resistance of daf-16 mutants, which are stress sensitive. Quantitative real-time PCR results also showed that the expression of two daf-16 target genes, hsp-12.3 and sod-3, was downregulated in EYA-1 RNAi-treated worms under stress. All this evidence indicates EYA-1 is required for stress resistance of worms, and it might act downstream of daf-16 to regulate expression of stress resistance-associated genes.

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Abbreviations

GFP:

green fluorescent protein

HSP-16.2:

heat-shock protein

NGM:

nematode growth medium

RNAi:

RNA interference

ROS:

reactive oxygen species

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Authors and Affiliations

  1. The State Engineering Laboratory of AIDS Vaccine, Jilin University, Changchun, P. R. China

    Bing-ying Wang, Yu-xiao Cui, Hua Wang, Ge Liu, Jun-feng Ma & Xue-qi Fu

  2. Key Laboratory for Molecular Enzymology and Engineering, Ministry of Education, Jilin University, Changchun, P. R. China

    Bing-ying Wang, Yu-xiao Cui, Hua Wang, Ge Liu, Jun-feng Ma & Xue-qi Fu

  3. China-Japan Union Hospital, Jilin University, Changchun, 130033, P. R. China

    Xue-song Xu

  4. Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, 73104, USA

    Zhizhuang Joe Zhao

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  1. Bing-ying Wang
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  2. Xue-song Xu
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  3. Yu-xiao Cui
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  4. Hua Wang
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  5. Ge Liu
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  6. Zhizhuang Joe Zhao
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  7. Jun-feng Ma
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Correspondence to Jun-feng Ma or Xue-qi Fu.

Additional information

Published in Russian in Biokhimiya, 2014, Vol. 79, No. 7, pp. 821–833.

Originally published in Biochemistry (Moscow) On-Line Papers in Press, as Manuscript BM14-063, June 1, 2014.

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Wang, By., Xu, Xs., Cui, Yx. et al. Caenorhabditis elegans eyes absent ortholog EYA-1 Is required for stress resistance. Biochemistry Moscow 79, 653–662 (2014). https://doi.org/10.1134/S0006297914070074

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  • DOI: https://doi.org/10.1134/S0006297914070074

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