TY - JOUR
T1 - Secretion of an Argonaute protein by a parasitic nematode and the evolution of its siRNA guides
AU - Chow, Franklin Wang Ngai
AU - Koutsovoulos, Georgios
AU - Ovando-Vázquez, Cesaré
AU - Neophytou, Kyriaki
AU - Bermúdez-Barrientos, Jose R.
AU - Laetsch, Dominik R.
AU - Robertson, Elaine
AU - Kumar, Sujai
AU - Claycomb, Julie M.
AU - Blaxter, Mark
AU - Abreu-Goodger, Cei
AU - Buck, Amy H.
N1 - Publisher Copyright:
© The Author(s) 2019.
PY - 2019/4/23
Y1 - 2019/4/23
N2 - Extracellular RNA has been proposed to mediate communication between cells and organisms however relatively little is understood regarding how specific sequences are selected for export. Here, we describe a specific Argonaute protein (exWAGO) that is secreted in extracellular vesicles (EVs) released by the gastrointestinal nematode Heligmosomoides bakeri, at multiple copies per EV. Phylogenetic and gene expression analyses demonstrate exWAGO orthologues are highly conserved and abundantly expressed in related parasites but highly diverged in free-living genus Caenorhabditis. We show that the most abundant small RNAs released from the nematode parasite are not microRNAs as previously thought, but rather secondary small interfering RNAs (siRNAs) that are produced by RNA-dependent RNA Polymerases. The siRNAs that are released in EVs have distinct evolutionary properties compared to those resident in free-living or parasitic nematodes. Immunoprecipitation of exWAGO demonstrates that it specifically associates with siRNAs from transposons and newly evolved repetitive elements that are packaged in EVs and released into the host environment. Together this work demonstrates molecular and evolutionary selectivity in the small RNA sequences that are released in EVs into the host environment and identifies a novel Argonaute protein as the mediator of this.
AB - Extracellular RNA has been proposed to mediate communication between cells and organisms however relatively little is understood regarding how specific sequences are selected for export. Here, we describe a specific Argonaute protein (exWAGO) that is secreted in extracellular vesicles (EVs) released by the gastrointestinal nematode Heligmosomoides bakeri, at multiple copies per EV. Phylogenetic and gene expression analyses demonstrate exWAGO orthologues are highly conserved and abundantly expressed in related parasites but highly diverged in free-living genus Caenorhabditis. We show that the most abundant small RNAs released from the nematode parasite are not microRNAs as previously thought, but rather secondary small interfering RNAs (siRNAs) that are produced by RNA-dependent RNA Polymerases. The siRNAs that are released in EVs have distinct evolutionary properties compared to those resident in free-living or parasitic nematodes. Immunoprecipitation of exWAGO demonstrates that it specifically associates with siRNAs from transposons and newly evolved repetitive elements that are packaged in EVs and released into the host environment. Together this work demonstrates molecular and evolutionary selectivity in the small RNA sequences that are released in EVs into the host environment and identifies a novel Argonaute protein as the mediator of this.
UR - http://www.scopus.com/inward/record.url?scp=85063076570&partnerID=8YFLogxK
U2 - 10.1093/nar/gkz142
DO - 10.1093/nar/gkz142
M3 - Journal article
C2 - 30820541
AN - SCOPUS:85063076570
SN - 0305-1048
VL - 47
SP - 3594
EP - 3606
JO - Nucleic Acids Research
JF - Nucleic Acids Research
IS - 7
ER -