A genetic pathway encoding double-stranded RNA transporters and interactors regulates growth and plasticity in Caenorhabditis elegans

The environment and genes shape the development, physiology and behaviour of organisms. Many animal species can take-up double-stranded RNA (dsRNA) from the environment. Environmental dsRNA changes gene expression through RNA interference (RNAi). While environmental RNAi is used as a laboratory tool, e.g. in nematodes, planaria and insects, its biological role remains enigmatic. Here we characterise the environmental dsRNA receptor SID-2 to understand the biological function of dsRNA uptake in Caenorhabditis elegans. First we determine that SID-2 localises to the apical membrane and the trans-Golgi-network (TGN) in the intestine, implicating the TGN as a central cellular compartment for environmental dsRNA uptake. We demonstrate that SID-2 is irrelevant for nucleotide uptake from the environment as a nutritional (nitrogen) source. Instead RNA profiling and high-resolution live imaging revealed a new biological function for sid-2 in growth and phenotypic plasticity. Surprisingly, lack of the ability to uptake environmental RNA reduces plasticity of gene expression. Furthermore, using genetic analyses we show that the dsRNA pathway genes sid-2, sid-1 and rde-4 together regulate growth. This work suggest that environmental RNA affects morphology and plasticity through gene regulation.