Physiol. Genomics AJP: Lung Cellular and Molecular Physiology
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Physiol. Genomics (July 2, 2002). doi:10.1152/physiolgenomics.00044.2002
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Articles in PresS, published online ahead of print June 27, 2002
Physiol Genomics, 10.1152/physiolgenomics.00044.2002
Submitted on April 16, 2002
Accepted on June 18, 2002

RNA interference of peroxisome-related genes in C. elegans - a new model for the human peroxisomal disorders

Oleh I Petriv1, David B Pilgrim2, Richard A Rachubinski1*, and Vladimir I Titorenko3

1 Department of Cell Biology, University of Alberta, Edmonton, Alberta, Canada
2 Department of Biological Sciences, University of Alberta, Edmonton, Alberta, Canada
3 Department of Cell Biology, University of Alberta, Edmonton, Alberta, Canada; Department of Biology, Concordia University, Montreal, Quebec, Canada

* To whom correspondence should be addressed. E-mail: rick.rachubinski{at}ualberta.ca.

RNA-mediated interference (RNAi) for the post-transcriptional silencing of genes was used to evaluate the importance of various peroxisomal enzymes and peroxins for the development of Caenorhabditis elegans and to compare the roles of these proteins in the nematode to their roles in yeasts and humans. The nematode counterparts of the human ATP-binding cassette half-transporters, the enzymes alkyldihydroxyacetonephosphate synthase and {Delta}3,5-{Delta}2,4-dienoyl-CoA isomerase, the receptors for peroxisomal membrane and matrix proteins (Pex19p and Pex5p), and components of the docking and translocation machineries for matrix proteins (Pex13p and Pex12p) are essential for the development of C. elegans. Unexpectedly, RNAi silencing of the acyl-CoA synthetase-mediated activation of fatty acids, the {alpha}- and ß-oxidation of fatty acids, the intraperoxisomal decomposition of hydrogen peroxide, and the peroxins Pex1p, Pex2p and Pex6p had no apparent effect on C. elegans development. The described analysis of functional gene knockouts through RNAi provides a basis for the use of C. elegans as a valuable model system with which to study the molecular and physiological defects underlying the human peroxisomal disorders.




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