RNA interference of peroxisome-related genes in C. elegans: a new model for human peroxisomal disorders.
RNA-mediated interference (RNAi) for the posttranscriptional 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 beta-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.
Department of Cell Biology, University of Alberta, Edmonton T6G 2H7, Canada.
Oleh I
OI
Petriv
David B
DB
Pilgrim
Richard A
RA
Rachubinski
Vladimir I
VI
Titorenko
D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D000101:Acetyl-CoA C-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D019883:Alkyl and Aryl Transferases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D017173:Caenorhabditis elegans / Q000201:enzymology / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D019748:Carbon-Carbon Double Bond Isomerases / Q000235:genetics / Q000378:metabolism; D002374:Catalase / Q000235:genetics / Q000378:metabolism; D003066:Coenzyme A Ligases / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D020868:Gene Silencing; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D016296:Mutagenesis; D018901:Peroxisomal Disorders / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D020675:Peroxisomes / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism
D018528:ATP-Binding Cassette Transporters; D029742:Caenorhabditis elegans Proteins; D008565:Membrane Proteins; D011993:Recombinant Fusion Proteins; D002374:Catalase; D000101:Acetyl-CoA C-Acetyltransferase; D019883:Alkyl and Aryl Transferases; C019654:alkylglycerone-phosphate synthase; D019748:Carbon-Carbon Double Bond Isomerases; C085575:delta(3,5),delta(2,4)-dienoyl-CoA isomerase; D003066:Coenzyme A Ligases