title: ATP-binding cassette transporters are required for efficient RNA interference in Caenorhabditis elegans.
abstract: RNA interference (RNAi) is a conserved gene-silencing phenomenon that can be triggered by delivery of double-stranded RNA (dsRNA) to cells and is a widely exploited technology in analyses of gene function. Although a number of proteins that facilitate RNAi have been identified, current descriptions of RNAi and interrelated mechanisms are far from complete. Here, we report that the Caenorhabditis elegans gene haf-6 is required for efficient RNAi. HAF-6 is a member of the ATP-binding cassette (ABC) transporter gene superfamily. ABC transporters use ATP to translocate small molecule substrates across the membranes in which they reside, often against a steep concentration gradient. Collectively, ABC transporters are involved in a variety of activities, including protective or barrier mechanisms that export drugs or toxins from cells, organellar biogenesis, and mechanisms that protect against viral infection. HAF-6 is expressed predominantly in the intestine and germline and is localized to intracellular reticular organelles. We further demonstrate that eight additional ABC genes from diverse subfamilies are each required for efficient RNAi in C. elegans. Thus, the ability to mount a robust RNAi response to dsRNA depends upon the deployment of two ancient systems that respond to environmental assaults: RNAi mechanisms and membrane transport systems that use ABC proteins.
authors.affiliation: Department of Molecular Biosciences, University of Kansas, Lawrence, KS 66045, USA.
authors.forename: Prema
authors.initials: P
authors.lastname: Sundaram
authors.forename: Benjamin
authors.initials: B
authors.lastname: Echalier
authors.forename: Wang
authors.initials: W
authors.lastname: Han
authors.forename: Dawn
authors.initials: D
authors.lastname: Hull
authors.forename: Lisa
authors.initials: L
authors.lastname: Timmons
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000483:Alleles; D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D017930:Genes, Reporter; D050505:Mutant Proteins / Q000378:metabolism; D010641:Phenotype; D021381:Protein Transport; D034622:RNA Interference; D012330:RNA, Double-Stranded / Q000235:genetics
chemical_list: D018528:ATP-Binding Cassette Transporters; D029742:Caenorhabditis elegans Proteins; D050505:Mutant Proteins; D012330:RNA, Double-Stranded; C121027:SMG-2 protein, C elegans