Research:
Systemic RNAi and intercellular RNA transport We are interested in the mechanisms of intercellular RNA transport that supports systemic RNAi in C. elegans and are investigating the developmental and signaling defects associated with mutations in these RNA transport proteins in C. elegans and mice. A remarkable property of RNA interference (RNAi) in C. elegans is its association with intercellular RNA transport pathways. This linkage mobilizes dsRNA-silencing signals and enables silencing to spread from the site of initiation throughout the animal and to the progeny. This phenomenon, known as systemic RNAi, is a conserved process among many multicellular organisms. Through genetic analysis, we have isolated systemic RNAi defective mutants (sid) and have identified the corresponding proteins (SID). SID-1 is a widely conserved dsRNA channel that selectively and specifically transports dsRNA into cells and is essential for systemic RNAi. A mammalian SID-1 homolog has been implicated in cytoplasmic delivery of modified siRNAs, suggesting that dsRNA transport is a conserved function for this family of channel proteins. SID-2 is a putative dsRNA receptor that is expressed and localized exclusively to the luminal membrane of the intestine. SID-2 transports ingested dsRNA across the intestinal epithelium into the animal to trigger RNAi. This process of sequence-specific gene silencing in response to environmentally-encountered dsRNA, known as environmental RNAi, is widespread throughout nature, including in mammals. The long-term objective of our research is to understand the physiological importance and mechanism of intercellular RNA transport in animals.
Selected Publications: Jose AM, Smith JJ, Hunter CP. Export of RNA silencing from C. elegans tissues does not require the RNA channel SID-1. Proc Natl Acad Sci U S A. 2009 106(7):2283-8. Shih JD, Fitzgerald MC, Sutherlin M, Hunter CP. The SID-1 double-stranded RNA transporter is not selective for dsRNA length. RNA. 2009 15(3):384-90. Whangbo JS, Hunter CP. Environmental RNA interference. Trends Genet. 2008 24(6):297-305. Jose AM, Hunter CP. Transport of sequence-specific RNA interference information between cells. Annu Rev Genet. 2007 41:305-30. Winston WM, Sutherlin M, Wright AJ, Feinberg EH, Hunter CP. Caenorhabditis elegans SID-2 is required for environmental RNA interference. Proc Natl Acad Sci U S A. 2007 104(25):10565-70. Schott DH, Cureton DK, Whelan SP, Hunter CP. An antiviral role for the RNA interference machinery in Caenorhabditis elegans. Proc Natl Acad Sci U S A. 2005 102(51):18420-4. Feinberg EH, Hunter CP. Transport of dsRNA into cells by the transmembrane protein SID-1. Science. 2003 301(5639):1545-7. Winston WM, Molodowitch C, Hunter CP. Systemic RNAi in C. elegans requires the putative transmembrane protein SID-1. Science. 2002 295(5564):2456-9. Hunter CP. Gene silencing: shrinking the black box of RNAi. Curr Biol. 2000 10(4):R137-40. Hunter CP. Genetics: a touch of elegance with RNAi. Curr Biol. 1999 9(12):R440-2. |
