Mice Deficient for a Small Cluster of Piwi-Interacting RNAs Implicate Piwi-Interacting RNAs in Transposon Control1

Abstract

The mammalian testis expresses a class of small noncoding RNAs that interact with mammalian PIWI proteins. In mice, the PIWI-interacting RNAs (piRNAs) partner with mammalian PIWI proteins, PIWIL1 and PIWIL2, also known as MIWI and MILI, to maintain transposon silencing in the germline genome. Here, we demonstrate that inactivation of Nct1/2, two noncoding RNAs encoding piRNAs, leads to derepression of LINE-1 (L1) but does not affect mouse viability, spermatogenesis, testicular gene expression, or fertility. These findings indicate that piRNAs from a cluster on chromosome 2 are necessary to maintain transposon silencing.

Impairment of Pachytene Spermatogenesis inDmrt7Deficient Mice, Possibly Causing Meiotic Arrest

“…25,32,33) Xu et al reported a 1.6-fold increase in the expression of LINE-1 in mice when they deleted the gene coding for specific piRNA. 34) We suspect that the increase in the expression of retrotransposons aborted spermatogenesis, but the increase was about 2-fold (Fig. 4A), lower than those reported for other genes, whose knockout caused overexpression of retrotransposons and spermatogenesis arrest.…”

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

“…Although pachytene piRNAs are relatively depleted of retrotransposons (Watanabe et al 2006;Reuter et al 2011), a partial deletion of a pachytene piRNA cluster was reported to derepress LINE-1 ORF1 proteins (Xu et al 2008). Furthermore, disruption of PIWIL1 catalytic activity causes increased accumulation of LINE1 retrotransposon transcripts (Reuter Testes were obtained at 5 wk after birth from Gt(ROSA)26Sor mice with either EGFP-neo or EGFP-Dneo, or without these sequences.…”

“…However, since only 17%-20% of the total pachytene piRNAs corresponds to retrotransposons (Aravin et al 2006;Girard et al 2006;Grivna et al 2006a;Lau et al 2006;Watanabe et al 2006), their role in retrotransposon silencing is less clear. A partial deletion of a pachytene piRNA cluster, however, was reported to result in increased expression of LINE-1 ORF1 proteins (Xu et al 2008). A more recent study showed that disruption of PIWIL1 catalytic activity causes accumulation of LINE1 retrotransposon transcripts in postnatal germ cells (Reuter et al 2011).…”

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

“…Germ cells in Miwi-deficient mice testis undergo meiosis without elongated spermatids or mature spermatozoa production [205]. Furthermore, the small non-coding RNAs Nct1 and Nct2 have recently been suggested to be piRNA precursors and are expressed particularly in pachytene spermatocytes [206], which also points to a role of piRNAs in the regulation of the meiotic stage in spermatogenesis. Although, Nct1 and Nct2-deficient mice display a decrease in a small cluster of piRNAs located on chromosome 2, it does not affect mouse spermatogenesis or fertility, suggesting that those piRNAs located on chromosome 2 are necessary to maintain transposon silencing [202].…”