@article {Raman066415, author = {Pravrutha Raman and Soriayah M Zaghab and Edward C Traver and Antony M Jose}, title = {Ingested double-stranded RNA and their mobile RNA derivatives have different requirements for gene silencing in C. elegans}, elocation-id = {066415}, year = {2016}, doi = {10.1101/066415}, publisher = {Cold Spring Harbor Laboratory}, abstract = {Double-stranded RNA (dsRNA) can cause specific gene silencing upon ingestion in many invertebrates and is being developed as a pesticide to target essential genes in animal pests. Silencing by ingested dsRNA is best understood in the worm C. elegans, where ingested dsRNA is recruited into the RNA interference (RNAi) pathway by the dsRNA-binding protein RDE-4 for eventual gene silencing by Argonaute proteins. Although silencing is thought to rely on both the ingested dsRNA and on additional dsRNA-derived RNAs called mobile RNAs that are transported between cells, the specific forms of RNA that enter different tissues and the proteins they engage to cause silencing are unclear. We found that when RDE-4 was expressed at high levels within a somatic tissue, silencing by ingested dsRNA could occur in rde-4(-) somatic tissues but not in the rde-4(-) germline. Consistent with the spread of dsRNA-derived mobile RNAs between cells, silencing was more efficient in rde-4(-) cells located near rde-4(+) cells. Surprisingly, silencing by mobile RNAs derived from ingested dsRNA could bypass the requirement for a nuclear Argonaute that both ingested dsRNA and mobile RNAs derived from neuronal dsRNA require for silencing the same target gene. Furthermore, silencing by mobile RNAs could bypass inhibition of silencing within a tissue that can be caused by expression from repetitive DNA in that tissue. These results identify possible mechanisms that animals can use to evade RNAi and suggest that mobile RNA derivatives of ingested dsRNA can bypass these resistance mechanisms and cause gene silencing.}, URL = {https://www.biorxiv.org/content/early/2016/07/28/066415}, eprint = {https://www.biorxiv.org/content/early/2016/07/28/066415.full.pdf}, journal = {bioRxiv} }