Biogenesis and germline functions of piRNAs

Abstract

Small interfering RNAs and microRNAs are generated from double-stranded RNA precursors by the Dicer endonucleases, and function with Argonaute-family proteins to target transcript destruction or to silence translation. A distinct class of 24- to 30-nucleotide-long RNAs, produced by a Dicer-independent mechanism, associates with Piwi-class Argonaute proteins. Studies in flies, fish and mice implicate these Piwi-associated RNAs (piRNAs)in germline development, silencing of selfish DNA elements, and in maintaining germline DNA integrity. However, whether piRNAs primarily control chromatin organization, gene transcription, RNA stability or RNA translation is not well understood, neither is piRNA biogenesis. Here, we review recent studies of piRNA production and function, and discuss unanswered questions about this intriguing new class of small RNAs.

Dicer independent small RNAs associate with telomeric heterochromatin

“…Profound strand asymmetry of some piRNAs and their lack of Dicer dependence prompt the view that piRNAs are not generated from dsRNA precursors. Instead, a ping-pong model involving single strand RNA transcripts was proposed for the generation of piRNAs in Drosophila, as well as prepachytene piRNAs in mice (Aravin et al 2007a;Hartig et al 2007;Klattenhoff and Theurkauf 2008). Heterogeneous singlestrand noncoding RNA transcripts (TelRNA or TERRA) were reported to associate with telomeres in mice (Horard and Gilson 2008).…”

“…They are derived from double-stranded RNA (dsRNA) precursors in a Dicer-dependent pathway and widely distributed in germ line and somatic cells (Stadler and Ruohola-Baker 2008). In contrast, piRNAs are longer (24-30 nt), associated with Piwi-subfamily proteins, and derived from single stranded RNAs (ssRNA) by a Dicerindependent mechanism (Aravin et al 2007a;Klattenhoff and Theurkauf 2008). piRNAs in mammals have only been reported in the male germ line (Aravin et al 2006;Girard et al 2006;Lau et al 2006;Aravin et al 2007b).…”

A multi-faceted approach to understanding male infertility: gene mutations, molecular defects and assisted reproductive techniques (ART)

“…Not only are they DICER-independent, they are also distinct from miRNAs in their length (24-30 nucleotides) and expression patterns. They are expressed particularly in pachytene spermatocytes and round spermatids during spermatogenesis, indicative of a role of these small RNAs in development and protection of male germ cells from invasive transposable elements [201]. The piRNAs repress retrotransposons and regulate at the posttranscriptional level.…”

Targeted gene silencing in mouse germ cells by insertion of a homologous DNA into a piRNA generating locus

“…To secure the genome of future generations from de novo insertion mutations, transposable elements should be tightly controlled in germ cells. The PIWI family proteins and their associated small RNAs, called PIWI-interacting RNAs (piRNAs), constitute an evolutionarily conserved defense system to control transposable elements in germ cells (Klattenhoff and Theurkauf 2008;Siomi et al 2011;Pillai and Chuma 2012). In Drosophila, zebrafish, and Xenopus, a majority of piRNAs has sequences corresponding to transposable elements including retrotransposons (Vagin et al 2006), and mutations in genes encoding the piRNA pathway components result in their derepression.…”