A conserved PHD finger protein and endogenous RNAi modulate insulin signaling in caenorhabditis elegans

Mansisidor, A.R.; Cecere, G.; Hoersch, S.; Jensen, M.B.; Kawli, T.; Kennedy, L.M.; Chavez, V.; Tan, M.W.; Lieb, J.D.; Grishok, A.

A conserved PHD finger protein and endogenous RNAi modulate insulin signaling in caenorhabditis elegans

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Item Type:	Article
Title:	A conserved PHD finger protein and endogenous RNAi modulate insulin signaling in caenorhabditis elegans
Creators Name:	Mansisidor, A.R., Cecere, G., Hoersch, S., Jensen, M.B., Kawli, T., Kennedy, L.M., Chavez, V., Tan, M.W., Lieb, J.D. and Grishok, A.
Abstract:	Insulin signaling has a profound effect on longevity and the oxidative stress resistance of animals. Inhibition of insulin signaling results in the activation of DAF-16/FOXO and SKN-1/Nrf transcription factors and increased animal fitness. By studying the biological functions of the endogenous RNA interference factor RDE-4 and conserved PHD zinc finger protein ZFP-1 (AF10), which regulate overlapping sets of genes in Caenorhabditis elegans, we identified an important role for these factors in the negative modulation of transcription of the insulin/PI3 signaling-dependent kinase PDK-1. Consistently, increased expression of pdk-1 in zfp-1 and rde-4 mutants contributed to their reduced lifespan and sensitivity to oxidative stress and pathogens due to the reduction in the expression of DAF-16 and SKN-1 targets. We found that the function of ZFP-1 in modulating pdk-1 transcription was important for the extended lifespan of the age-1(hx546) reduction-of-function PI3 kinase mutant, since the lifespan of the age-1; zfp-1 double mutant strain was significantly shorter compared to age-1(hx546). We further demonstrate that overexpression of ZFP-1 caused an increased resistance to oxidative stress in a DAF-16-dependent manner. Our findings suggest that epigenetic regulation of key upstream signaling components in signal transduction pathways through chromatin and RNAi may have a large impact on the outcome of signaling and expression of numerous downstream genes.
Keywords:	Caenorhabditis elegans, Genetic Epigenesis, Gene Expression Regulation, Insulin, Longevity, Oxidative Stress, Paraquat, Phosphatidylinositol 3-Kinases, RNA-Binding Proteins, RNA Interference, Signal Transduction, Transcription Factors, Animals
Source:	PLoS Genetics
ISSN:	1553-7390
Publisher:	Public Library of Science
Volume:	7
Number:	9
Page Range:	e1002299
Date:	September 2011
Official Publication:	https://doi.org/10.1371/journal.pgen.1002299
PubMed:	View item in PubMed

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