Conserved themes in small-RNA-mediated transposon control

Abstract

Eukaryotes are engaged in a constant struggle against transposable elements, which have invaded and profoundly shaped their genomes. Over the past decade, a growing body of evidence has pointed to a role for small RNAs in transposon defense. Although the strategies used in different organisms vary in their details, they have strikingly similar general properties. Basically, all mechanisms consist of three components. First, transposon detection prompts the production of small RNAs, which are Piwi-interacting RNAs in some organisms and small interfering RNAs in others. Second, the population of small RNAs targeting active transposons is amplified through an RNA-dependent RNA polymerase-based or Slicer-based mechanism. Third, small RNAs are incorporated into Argonaute- or Piwi-containing effector complexes, which target transposon transcripts for post-transcriptional silencing and/or target transposon DNA for repressive chromatin modification and DNA methylation. These properties produce robust systems that limit the catastrophic consequences of transposon mobilization, which can result in the accumulation of deleterious mutations, changes in gene expression patterns, and conditions such as gonadal hypotrophy and sterility.

Figure I

The siRNA pathway.

Figure I

The Argonaute protein family. Abbreviations: ath, Arabidopsis thaliana; cel, Caenorhabditis elegans; dme, Drosophila melanogaster; hsa, Homo sapiens; mmu, Mus musculus; ncr, Neurospora crassa; spo, Schizosaccharomyces pombe; tth, Tetrahymena thermophila.

Figure 1

Eukaryotic small RNA-based transposon silencing relies on three linked steps: detection, amplification and repression. (a) (i) In animals, 24–30-nucleotide primary piRNAs are processed from long RNA precursors transcribed from defined loci called piRNA clusters. Any transposon inserted in the reverse orientation in the piRNA cluster can give rise to antisense piRNAs (in red). (ii) Antisense piRNAs are incorporated into a Piwi protein (in flies, this is mostly Aubergine or Piwi) and direct its Slicer activity on sense transposon transcripts. The 3′ cleavage product is bound by another Piwi protein (Ago3 in flies) and trimmed to piRNA size. This sense piRNA is in turn used to cleave piRNA cluster transcripts and to generate more antisense piRNAs. (iii) Eventually, antisense piRNAs can target the Piwi complexes to cDNA for DNA methylation and/or histone modification. (b) (i) In plants and S. pombe, transposon expression leads to dsRNA formation, through a process that is still largely unexplained. One possible source of dsRNA is the read-through transcription of inverted repeats. Another is the synthesis of the reverse strand from transposon RNA templates by an RDRP. This dsRNA is then processed into 21–24-nucleotide small RNAs by a Dicer protein. (ii) Transposon-derived siRNAs can then bind an Argonaute protein and direct cleavage of transposon transcripts. These cleaved RNAs are potential templates for RDRP-mediated reverse strand synthesis and processing of more siRNAs by Dicer. (iii) As in animals, siRNA-Argonaute complexes can target DNA and histone-modifying complexes to cDNA sequences.