Systemic RNAi in Caenorhabditis elegans

  1. C.P. HUNTER,
  2. W.M. WINSTON,
  3. C. MOLODOWITCH,
  4. E.H. FEINBERG,
  5. J. SHIH,
  6. M. SUTHERLIN,
  7. A.J. WRIGHT, and
  8. M.C. FITZGERALD
  1. Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138

Abstract

RNA interference (RNAi) in Caenorhabditis elegans induced by ingestion or injection of double-stranded RNA (dsRNA)spreads throughout the organism and is even transmitted to the progeny. We have identified two proteins required for spreadingof RNAi, SID-1 and SID-2, whose structure, subcellular localization, and expression pattern have been informative forhow dsRNA can be transported into and between cells. SID-1 is a transmembrane protein that functions as a pore or channelthat transports dsRNA into and out of cells. Proteins homologous to SID-1 are present in a wide range of invertebrate andvertebrate animals but are absent from plants. SID-2 is a small transmembrane protein that is expressed in the gut and localizesstrongly to the luminal membrane where it appears to act as a receptor for uptake of dsRNA from the environment.Characterization of SID-2 activity in a variety of Caenorhabditis nematodes indicates that C. elegans SID-2 may have a novelactivity.

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