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Vol. 17, Issue 8, 3678-3688, August 2006

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ATP-binding Cassette Transporters Are Required for Efficient RNA Interference in Caenorhabditis elegans

Prema Sundaram^*, Benjamin Echalier^*,, Wang Han, Dawn Hull, and Lisa Timmons

Department of Molecular Biosciences, University of Kansas, Lawrence, KS 66045

Submitted March 13, 2006; Revised May 4, 2006; Accepted May 11, 2006
Monitoring Editor: Marvin P. Wickens

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.

The online version of this article contains supplemental material at MBC Online (http://www.molbiolcell.org).

* These authors contributed equally to this work.

Present addresses: Department of Plant Pathology, Kansas State University, Manhattan, KS 66506;

Biomune Company, Lenexa, KS 66215.

Address correspondence to: Lisa Timmons ( timmons{at}ku.edu)

Abbreviations used: ABC, ATP-binding cassette; dsRNA, double-stranded RNA; RNAi, RNA interference.

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