PT  - JOURNAL ARTICLE
AU  - Snusha Ravikumar
AU  - Sindhuja Devanapally
AU  - Antony M Jose
TI  - Gene silencing by double-stranded RNA from <em>C. elegans</em> neurons reveals functional mosaicism of RNA interference
AID  - 10.1101/393074
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 393074
4099  - http://biorxiv.org/content/early/2018/08/16/393074.short
4100  - http://biorxiv.org/content/early/2018/08/16/393074.full
AB  - 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, organism-wide silencing relies on the transport of dsRNA to cells and requires amplification of silencing signals. Amplification in somatic cells is thought to occur through the production of small RNAs by the RNA-dependent RNA Polymerase RRF-1. Here we show that the requirement for RRF-1 can vary based on the source of dsRNA, the target context, and even the particular cell examined. When the same intestinal target gene is silenced using ingested, intracellular, or neuronal dsRNA, only silencing by neuronal dsRNA is independent of RRF-1. When neuronal dsRNA is used to silence the same target sequence fused to different genes, the requirement for RRF-1 can differ. When both source and target are kept constant, different sets of intestinal cells show silencing in the absence of RRF-1 in different animals. Thus, the unequal and random availability of factor(s) that can compensate for the absence of RRF-1 in somatic cells suggests that each C. elegans animal is a functional mosaic with respect to RNA interference.GRAPHICAL ABSTRACT Double-stranded RNA (dsRNA) from neurons can bypass the requirement for the RNA-dependent RNA Polymerase RRF-1 to cause gene silencing in varying sets of intestinal cells.