Abstract
Small RNAs are important regulators of gene expression. They were first identified in Caenorhabditis elegans, but it is now apparent that the main small RNA silencing pathways are functionally conserved across diverse organisms. Availability of genome data for an increasing number of parasitic nematodes has enabled bioinformatic identification of small RNA sequences. Expression of these in different lifecycle stages is revealed by small RNA sequencing and microarray analysis. In this review we describe what is known of the three main small RNA classes in parasitic nematodes - microRNAs (miRNAs), Piwi-interacting RNAs (piRNAs) and small interfering RNAs (siRNAs) - and their proposed functions. miRNAs regulate development in C. elegans and the temporal expression of parasitic nematode miRNAs suggest modulation of target gene levels as parasites develop within the host. miRNAs are also present in extracellular vesicles released by nematodes in vitro, and in plasma from infected hosts, suggesting potential regulation of host gene expression. Roles of piRNAs and siRNAs in suppressing target genes, including transposable elements, are also reviewed. Recent successes in RNAi-mediated gene silencing, and application of small RNA inhibitors and mimics will continue to advance understanding of small RNA functions within the parasite and at the host-parasite interface.
Highlights
Knowledge of small RNA structure and function has increased greatly in the last decade
The above features of C. elegans Piwi-interacting RNAs (piRNAs) are conserved in the clade V parasitic nematodes in which they have been identified, including Pristionchus pacificus, H. contortus, H. polygyrus and Nippostrongylus brasiliensis, based on small RNA sequencing and genome data, their organization is different
Our work in H. contortus showed that while some genes could be silenced using the soaking method, this was most effective for genes expressed in sites accessible to the environment, such as the gut, amphids and excretory cell. This suggested limited uptake and/or spreading of double-stranded RNA (dsRNA) in the non-feeding infective L3 stage used (Samarasinghe et al, 2011). This was supported by comparative genomic studies showing that while most genes required for small interfering RNAs (siRNAs)-mediated gene silencing can be identified in parasitic nematodes (Dalzell et al, 2011; reviewed in Britton et al, 2016), a homologue of the transmembrane transporter SID-2, required for environmental RNA interference (RNAi) in C. elegans (Winston et al, 2007), was absent in parasitic species
Summary
Knowledge of small RNA structure and function has increased greatly in the last decade. For parasitic species, sequencing or microarray analysis can identify miRNAs expressed in different lifecycle stages, to help determine their roles in regulating development.
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