![]() Argonaute proteins play a central role in binding to small RNAs and silencing of complementary transcripts in the cell by either destroying them or preventing their correct translation. The diversity of RNAi appears to be linked to the presence of multiple paralogues of these RNAi-genes and a complex subset of accessory proteins. Notwithstanding the enormous complexity of RNAi, only three key protein components are well-conserved in eukaryotes, namely Argonaute proteins, RNA-dependent RNA-polymerases (RdRPs) and Dicer-like enzymes 6. A third group are the piwi-interacting (pi)RNAs, which help maintain the genome stability through silencing of selfish nucleic acids, like transposons 3– 5. 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. There are three major branches of small RNAs. One of the most important and best-described groups of regulatory RNAs are the small RNAs, which trigger gene silencing through the RNA interference (RNAi) pathway 2. 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.Ī large portion of the RNA-species in Metazoans is not translated into proteins, but plays a role in controlling the cellular protein levels 1. Interestingly, we also demonstrate that vertebrates lack siRNA-class AGO proteins and that vertebrate AGOs display low rates of molecular evolution. 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. 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. The animal Argonaute superfamily is traditionally grouped into AGO and PIWI Argonautes. ![]() 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). 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. ![]()
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