Functional diversification of Argonautes in nematodes: an expanding universe

Amy H Buck,Mark Blaxter

doi:10.1042/bst20130086

Abstract

In the last decade, many diverse RNAi (RNA interference) pathways have been discovered that mediate gene silencing at epigenetic, transcriptional and post-transcriptional levels. The diversity of RNAi pathways is inherently linked to the evolution of Ago (Argonaute) proteins, the central protein component of RISCs (RNA-induced silencing complexes). An increasing number of diverse Agos have been identified in different species. The functions of most of these proteins are not yet known, but they are generally assumed to play roles in development, genome stability and/or protection against viruses. Recent research in the nematode Caenorhabditis elegans has expanded the breadth of RNAi functions to include transgenerational epigenetic memory and, possibly, environmental sensing. These functions are inherently linked to the production of secondary siRNAs (small interfering RNAs) that bind to members of a clade of WAGOs (worm-specific Agos). In the present article, we review briefly what is known about the evolution and function of Ago proteins in eukaryotes, including the expansion of WAGOs in nematodes. We postulate that the rapid evolution of WAGOs enables the exceptional functional plasticity of nematodes, including their capacity for parasitism.

Highlights

RNAi (RNA interference) was first described as the mechanism by which double-stranded RNA silences cognate sequences in nematodes [1], which paralleled earlier findings in plants showing that transgenes caused silencing of endogenous genes and this was mediated by RNA [2]
Small RNAs incorporated into RISCs include miRNAs, endogenous or exogenous small interfering RNA (siRNA), piRNAs and other transposon-associated small RNAs; these differ in their origins, subcellular localizations and/or presence in different tissues
Within the free-living C. elegans, and its relatives, a surprising diversity of small RNAs and small RNAmediated biological regulation has become apparent, and this is necessarily accompanied by a diversity in small RNA protein partners, including the Ago proteins

Summary

Introduction

RNAi (RNA interference) was first described as the mechanism by which double-stranded RNA silences cognate sequences in nematodes [1], which paralleled earlier findings in plants showing that transgenes caused silencing of endogenous genes and this was mediated by RNA [2] Since these discoveries, many versions of RNAi have been described in Eukarya, all of which involve RISCs (RNAinduced silencing complexes) minimally comprising one Ago (Argonaute) protein and one small RNA. Ago proteins have at least two important roles in RISCs: they must recognize and bind small RNAs and they must mediate interactions with other proteins required for loading small RNAs, association with targets, gene silencing activity and/or subcellular localization (reviewed in [5]). Ago-like proteins in plants can direct histone methylation (AtAgo4) as well

C The Authors Journal compilation C 2013 Biochemical Society

Conclusions