RNAi screening implicates a SKN-1-dependent transcriptional response in stress resistance and longevity deriving from translation inhibition

Wang, Jinling, Robida-Stubbs, Stacey, Tullet, Jennifer M.A., Rual, Jean-François, Vidal, Marc, Blackwell, T Keith (2010) RNAi screening implicates a SKN-1-dependent transcriptional response in stress resistance and longevity deriving from translation inhibition. PLoS genetics, 6 (8). pp. 1-17. ISSN 1553-7404. (doi:10.1371/journal.pgen.1001047) (The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided)

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Official URL
http://dx.doi.org/10.1371/journal.pgen.1001047

Abstract

Caenorhabditis elegans SKN-1 (ortholog of mammalian Nrf1/2/3) is critical for oxidative stress resistance and promotes longevity under reduced insulin/IGF-1-like signaling (IIS), dietary restriction (DR), and normal conditions. SKN-1 inducibly activates genes involved in detoxification, protein homeostasis, and other functions in response to stress. Here we used genome-scale RNA interference (RNAi) screening to identify mechanisms that prevent inappropriate SKN-1 target gene expression under non-stressed conditions. We identified 41 genes for which knockdown leads to activation of a SKN-1 target gene (gcs-1) through skn-1-dependent or other mechanisms. These genes correspond to multiple cellular processes, including mRNA translation. Inhibition of translation is known to increase longevity and stress resistance and may be important for DR-induced lifespan extension. One model postulates that these effects derive from reduced energy needs, but various observations suggest that specific longevity pathways are involved. Here we show that translation initiation factor RNAi robustly induces SKN-1 target gene transcription and confers skn-1-dependent oxidative stress resistance. The accompanying increases in longevity are mediated largely through the activities of SKN-1 and the transcription factor DAF-16 (FOXO), which is required for longevity that derives from reduced IIS. Our results indicate that the SKN-1 detoxification gene network monitors various metabolic and regulatory processes. Interference with one of these processes, translation initiation, leads to a transcriptional response whereby SKN-1 promotes stress resistance and functions together with DAF-16 to extend lifespan. This stress response may be beneficial for coping with situations that are associated with reduced protein synthesis.

Item Type: Article
DOI/Identification number: 10.1371/journal.pgen.1001047
Subjects: Q Science > Q Science (General)
Divisions: Faculties > Sciences > School of Biosciences
Depositing User: Jennifer Tullet
Date Deposited: 13 Oct 2014 08:19 UTC
Last Modified: 29 May 2019 13:09 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/43251 (The current URI for this page, for reference purposes)
Tullet, Jennifer M.A.: https://orcid.org/0000-0002-2037-526X
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