Secretion of an Argonaute protein by a parasitic nematode and the evolution of its siRNA guides
Secretion of an Argonaute protein by a parasitic nematode and the evolution of its siRNA guides
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DOI：
10.1093/nar/gkz142
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发表时间：
2019-04-23
影响因子：
14.9
通讯作者：
Buck, Amy H.
中科院分区：
文献类型：
--
作者：
Chow, Franklin Wang-Ngai;Koutsovoulos, Georgios;Buck, Amy H.
已经提出细胞外RNA介导细胞和生物体之间的通信，然而关于如何选择特定序列用于输出的理解相对较少。在这里，我们描述了一个特定的Argonaute蛋白（exWAGO），分泌在细胞外囊泡（EV）释放的胃肠道线虫Heligmosomoides bakeri，在多个拷贝每EV。系统发育和基因表达分析表明，exWAGO直系同源物是高度保守的，并在相关的寄生虫中大量表达，但在自由生活的小杆线虫属中高度分化。我们发现，从线虫寄生虫释放的最丰富的小RNA不是以前认为的microRNA，而是由RNA依赖性RNA聚合酶产生的次级小干扰RNA（siRNA）。在EV中释放的siRNA与自由生活或寄生线虫中的siRNA相比具有不同的进化特性。exWAGO的免疫沉淀表明，它特异性地与来自转座子和新进化的重复元件的siRNA相关联，这些元件被包装在EV中并释放到宿主环境中。总之，这项工作证明了在EV中释放到宿主环境中的小RNA序列的分子和进化选择性，并确定了一种新的Argonaute蛋白作为介体。
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.