SID-5 Is an Endosome-Associated Protein Required for Efficient Systemic RNAi in C. elegans
2012 (English)In: Current Biology, ISSN 0960-9822, E-ISSN 1879-0445, Vol. 22, no 20, 1938-1943 p.Article in journal (Refereed) Published
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-/-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.
Place, publisher, year, edition, pages
2012. Vol. 22, no 20, 1938-1943 p.
IdentifiersURN: urn:nbn:se:uu:diva-190350DOI: 10.1016/j.cub.2012.08.020ISI: 000311882600028OAI: oai:DiVA.org:uu-190350DiVA: diva2:585172