Caenorhabditis elegans Eyes Absent Ortholog EYA-1 Is Required for Stress Resistance

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Bing-ying Wang^1,2, Xue-song Xu³, Yu-xiao Cui^1,2, Hua Wang^1,2, Ge Liu^1,2, Zhizhuang Joe Zhao⁴, Jun-feng Ma^1,2*, and Xue-qi Fu^1,2*

¹The State Engineering Laboratory of AIDS Vaccine, Jilin University, Changchun, P. R. China; fax: 86-431-85155152; E-mail: mjf@jlu.edu.cn; fxq@jlu.edu.cn

²Key Laboratory for Molecular Enzymology and Engineering, Ministry of Education, Jilin University, Changchun, P. R. China; E-mail: wangbingyingicy@163.com; 363906218@qq.com; 253815665@qq.com; 874227993@qq.com

³China-Japan Union Hospital, Jilin University, Changchun 130033, P. R. China; E-mail: xuesongx@126.com

⁴Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104, USA; E-mail: joe-zhao@ouhsc.edu

^* To whom correspondence should be addressed.

Received March 8, 2014; Revision received April 2, 2014

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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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KEY WORDS: EYA-1, Caenorhabditis elegans, RNA interference, stress resistance

DOI: 10.1134/S0006297914070074

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