Argonaute protein PIWI controls mobilization of retrotransposons in the Drosophila male germline

Abstract

Proteins of the Argonaute family have been identified as key components of RNA interference (RNAi) pathway. RNAi-related mechanisms are implicated in the regulation of gene expression and repression of transposable elements in eukaryotes. The piwi gene encoding protein of the Drosophila Argonaute family was shown to be required for the germ stem cells maintenance. Here, we show that piwi is involved in silencing of LTR retrotransposons in testes. piwi mutations led to derepression of endogenous retrotransposon copia as well as to upregulation of the reporter gene driven by copia LTR. piwi mutation causes accumulation of retrotransposon mdg1 transcripts at the apical tip of testes, including germinal proliferative center where PIWI protein was shown to be expressed. We applied inverse PCR approach to detect the newly arisen insertions of the mdg1 retrotransposon in the progeny of individual piwi mutant males. Owing to piwi mutation a high rate of mdg1 transpositions was revealed. Thus, piwi is involved in the silencing of retrotransposons in the precursors of male gametes. Our results provide the first evidence that protein of the Argonaute family prevents retrotranspositions. It is supposed that the disturbance of RNA silencing system in germinal cells might cause transposition burst.

Drosophila Piwi functions downstream of piRNA production mediating a chromatin-based transposon silencing mechanism in female germ line

“…Transposon transposition creates DNA double-strand breaks; a DNA damage response can occur, leading to a checkpoint arrest and polarity specification defects. Indeed, Kalmykova et al have shown that the progeny of piwi mutants can exhibit new insertion sites for the mdg1 transposon (32). This report of actual transposition events provides strong evidence linking transposon activity with the polarity specification defects commonly observed in mutants deficient in piRNA pathway components and seen here.…”

Conserved themes in small-RNA-mediated transposon control

“…Drosophila melanogaster encodes three Piwi proteins: Piwi, Aub and Ago3; and Piwi and Aub have been genetically linked to transposon silencing [41,54,[82][83][84][85]. Although no mutant for Ago3 has been characterized, the Ago3 protein associates with repeatassociated piRNAs [43,77].…”

Separation of stem cell maintenance and transposon silencing functions of Piwi protein

“…Another role of Piwi in germ-line development is related to the formation of maternally inherited pole plasm (13). Finally, piwi mutations lead to transposable element overexpression and cause a transposition burst as a result of the loss of Piwi-interacting RNA (piRNA) silencing (14)(15)(16)(17)(18). Piwi is the founding member of the evolutionarily conserved piRNAbinding Piwi protein subfamily, which also includes Aub and Ago3 proteins in Drosophila (18).…”