title: Caenorhabditis elegans eyes absent ortholog EYA-1 is required for stress resistance.
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.
authors.affiliation: The State Engineering Laboratory of AIDS Vaccine, Jilin University, Changchun, P. R. China. mjf@jlu.edu.cn.
authors.forename: Bing-ying
authors.initials: BY
authors.lastname: Wang
authors.forename: Xue-song
authors.initials: XS
authors.lastname: Xu
authors.forename: Yu-xiao
authors.initials: YX
authors.lastname: Cui
authors.forename: Hua
authors.initials: H
authors.lastname: Wang
authors.forename: Ge
authors.initials: G
authors.lastname: Liu
authors.forename: Zhizhuang Joe
authors.initials: ZJ
authors.lastname: Zhao
authors.forename: Jun-feng
authors.initials: JF
authors.lastname: Ma
authors.forename: Xue-qi
authors.initials: XQ
authors.lastname: Fu
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D017173:Caenorhabditis elegans / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism / Q000502:physiology*; D051858:Forkhead Transcription Factors; D020043:Genes, Essential; D018869:Heat-Shock Response; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology*; D009687:Nuclear Proteins / Q000502:physiology*; D018384:Oxidative Stress; D017027:Protein Tyrosine Phosphatases / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; D051858:Forkhead Transcription Factors; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; C108831:daf-16 protein, C elegans; D017027:Protein Tyrosine Phosphatases; C506511:eya-1 protein, C elegans