RRC ID 46354
Author Hinas A, Wright AJ, Hunter CP.
Title SID-5 is an endosome-associated protein required for efficient systemic RNAi in C. elegans.
Journal Curr Biol
Abstract In the nematode C. elegans, RNAi silencing signals are efficiently taken up from the environment and transported between cells and tissues. Previous studies implicating endosomal proteins in systemic RNAi lack conclusive evidence. 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, thus expanding the systemic RNAi pathway.
Volume 22(20)
Pages 1938-43
Published 2012-10-23
DOI 10.1016/j.cub.2012.08.020
PII S0960-9822(12)00948-7
PMID 22981770
PMC PMC10518204
MeSH Animals Biological Transport Caenorhabditis elegans / genetics* Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* DNA / metabolism Endosomes / genetics Endosomes / metabolism Green Fluorescent Proteins / genetics Intestinal Mucosa / metabolism Membrane Glycoproteins / genetics Membrane Glycoproteins / metabolism* RNA Interference* RNA, Double-Stranded / metabolism RNA, Small Cytoplasmic Sequence Deletion rab GTP-Binding Proteins / metabolism* rab7 GTP-Binding Proteins
IF 9.601
Times Cited 54
C.elegans tm4328