Abstract
In addition to mediating regulation of endogenous gene expression, RNA interference (RNAi) in plants and invertebrates plays a crucial role in defense against viruses via virus-specific siRNAs. Different studies have demonstrated that the functional diversity of RNAi in animals is linked to the diversification of the Argonaute superfamily, central components of RISCs (RNA induced silencing complexes). The animal Argonaute superfamily is traditionally grouped into AGO and PIWI Argonautes. Yet, by performing phylogenetic analyses and determining the selective evolutionary pressure in the metazoan Argonaute superfamily, we provide evidence for the existence of three conserved Argonaute lineages between basal metazoans and protostomes, namely siRNA-class AGO, miRNA-class AGO and PIWI Argonautes. In addition, it shown that the siRNA-class AGO lineage is characterized by high rates of molecular evolution, suggesting a role in the arms race with viruses, while the miRNA-class AGOs display strong sequence conservation. Interestingly, we also demonstrate that vertebrates lack siRNA-class AGO proteins and that vertebrate AGOs display low rates of molecular evolution. In this way, we provide supportive evidence for the loss of the antiviral siRNA-class AGO group in vertebrates and discuss the consequence hereof on antiviral immunity and the use of RNAi as a loss of function tool in these animals.
Highlights
There are three major branches of small RNAs
Amino acid sequence identity between siRNA-class AGOs of C. elegans (Cel-RDE-1 and Cel-ERGO-1) and D. melanogaster (Dme-AGO2) is less than 15% and even AGO2 proteins belonging to different insect species have very low sequence identity
This article describes the discovery of three conserved Argonaute groups in invertebrates, miRNA-class AGOs with a primary function in endogenous gene regulation, the antiviral siRNA-class AGOs that are under strong selective pressure and PIWI Argonautes that mediate piRNA-directed transposon silencing
Summary
There are three major branches of small RNAs. Whereas genome encoded micro (mi)RNAs play a central role in the regulation of a multitude of cellular and physiological processes by induction of silencing of endogenous transcripts, short interfering (si)RNAs are derived from long exogenous dsRNA-fragments, typically produced during virus replication, and act as the defenders of the cell against invading viruses. Argonaute proteins found in animals are classified into three major groups, based on their interaction with specific small RNA species. Virus encoded suppressors of RNAi (VSRs) have been identified in mammalian viruses[20, 21] These recent findings reopened the debate on the existence of antiviral RNAi in mammals, and, more broadly, in vertebrates. It currently remains unclear to what extend viral-derived siRNAs contribute to the antiviral immune response in these animals
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