Gene silencing in Caenorhabditis elegans by transitive RNA interference

  1. MATTHEW N. ALDER,
  2. SHALE DAMES,
  3. JEFFREY GAUDET, and
  4. SUSAN E. MANGO
  1. Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah 84112, USA

Abstract

When a cell is exposed to double-stranded RNA (dsRNA), mRNA from the homologous gene is selectively degraded by a process called RNA interference (RNAi). Here, we provide evidence that dsRNA is amplified in Caenorhabditis elegans to ensure a robust RNAi response. Our data suggest a model in which mRNA targeted by RNAi functions as a template for 5′ to 3′ synthesis of new dsRNA (termed transitive RNAi). Strikingly, the effect is nonautonomous: dsRNA targeted to a gene expressed in one cell type can lead to transitive RNAi-mediated silencing of a second gene expressed in a distinct cell type. These data suggest dsRNA synthesized in vivo can mediate systemic RNAi.

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