Abstract

Vesicle and RNA Secretion by Helminths: At the Host Interface

Amy Buck, Assistant Professor, University of Edinburgh Medical School

The transport of RNA within extracellular vesicles (EVs) has been proposed as a means of cell-to-cell communication within an organism and a mechanism of cross-species communication. We study the functions of EVs and their RNA cargos in helminths, which are parasitic worms that naturally infect plants and animals, including ¼ of the human population. Helminths have co-evolved with their hosts’ immune systems for hundreds of millions of years and establish chronic infections through the secretion of bioactive molecules that modulate host cells. Helminth secretion products contain EVs that we have shown can suppress innate immune responses in vitro and in vivo. Proteomic analyses of the EVs derived from Heligomosomoides polygyrus, a gastrointestinal nematode that naturally infects mice, suggest these derive from the endocytic pathway and also reveal the presence of a newly evolved Argonaute protein in the EVs. Small RNA sequencing analyses demonstrate that miRNAs and Y RNAs are present in the EVs, but the dominant class of vesicular small RNA contains 5’triphosphates, most likely as a result of synthesis by an RNA-dependent RNA polymerase. A subset of these 5’ triphosphate nematode small RNAs are detected in mouse cells and l will discuss our recent work investigating their origins and properties.