In the nematode C. elegans, RNAi silencing signals are efficiently taken up from the environment and transported between cells and tissues [1-3]. Previous studies implicating endosomal proteins in systemic RNAi lack conclusive evidence [4, 5]. Here, we report the identification and characterization of SID-5, a C. elegans endosome-associated protein that is required for efficient systemic RNAi in response to both ingested and expressed double-stranded RNA (dsRNA). SID-5 is detected in cytoplasmic foci that partially colocalize with GFP fusions of late endosomal proteins RAB-7 and LMP-1. Furthermore, knockdown of various endosomal proteins similarly relocalizes both SID-5 and LMP-1::GFP. Consistent with a non-cell-autonomous function, intestine-specific SID-5 expression restored body wall muscle (bwm) target gene silencing in response to ingested dsRNA. Finally, we show that sid-5 is required for the previously described sid-1-independent transport of ingested RNAi triggers across the intestine . Together, these data demonstrate that an endosome-associated protein, SID-5, promotes the transport of RNAi silencing signals between cells. Furthermore, SID-5 acts differently than the previously described SID-1, SID-2, and SID-3 proteins [3, 6-8], thus expanding the systemic RNAi pathway. © 2012 Elsevier Ltd.
Hinas, A., Wright, A. J., & Hunter, C. P. (2012). SID-5 Is an Endosome-Associated Protein Required for Efficient Systemic rnai in C. Elegans. Current Biology, 22(20), 1938–1943. https://doi.org/10.1016/j.cub.2012.08.020