Gene silencing by double-stranded RNA from C. elegans neurons reveals functional mosaicism of RNA interference

Delivery of double-stranded RNA (dsRNA) into animals can silence genes of matching sequence in diverse cell types through mechanisms that have been collectively called RNA interference. In the nematode C. elegans, dsRNA from multiple sources can trigger the amplification of silencing signals. Amplification occurs through the production of small RNAs by two RNA-dependent RNA polymerases (RdRPs) that are thought to be tissue-specific - EGO-1 in the germline and RRF-1 in somatic cells. Here we analyze instances of silencing in somatic cells that lack RRF-1. By varying dsRNA sources and target genes, we find that silencing in the absence of RRF-1 is most obvious when dsRNA from neurons is used to silence genes in intestinal cells. This silencing requires EGO-1, but the lineal identity of cells that can use EGO-1 varies. This variability could be because random sets of cells can either receive different amounts of dsRNA from the same source or use different RdRPs to perform the same function. As a result, all cells appear similarly functional despite underlying differences that vary from animal to animal. This functional mosaicism cautions against the use of a few molecules as proxies for predicting the behavior of a cell.\n\nGraphical Abstract\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=143 SRC=\"FIGDIR/small/393074v2_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (29K):\norg.highwire.dtl.DTLVardef@f61659org.highwire.dtl.DTLVardef@3535c2org.highwire.dtl.DTLVardef@15c59d0org.highwire.dtl.DTLVardef@ca4ef_HPS_FORMAT_FIGEXP M_FIG C_FIG Random sets of cells can either receive different amounts of double-stranded RNA from neurons or use different RdRPs - RRF-1 only versus RRF-1 or EGO-1 - to perform the same function.