Restricted and non-essential redundancy of RNAi and piRNA pathways in mouse oocytes

Abstract

Germline genome defense evolves to recognize and suppress retrotransposons. One of defensive mechanisms is the PIWI-associated RNA (piRNA) pathway, which employs small RNAs for sequence-specific repression. The loss of the piRNA pathway in mice causes male sterility while females remain fertile. Unlike spermatogenic cells, mouse oocytes posses also RNA interference (RNAi), another small RNA pathway capable of retrotransposon suppression. To examine whether RNAi compensates the loss of the piRNA pathway, we produced a new RNAi pathway mutant Dicer SOM and crossed it with a catalytically-dead mutant of Mili, an essential piRNA gene. Normal follicular and oocyte development in double mutants showed that RNAi does not suppress a strong ovarian piRNA knock-out phenotype. However, we observed redundant and non-redundant targeting of specific retrotransposon families illustrating stochasticity of recognition and targeting of invading retrotransposons. Intracisternal A Particle retrotransposon was mainly targeted by the piRNA pathway, MaLR and RLTR10 retrotransposons were targeted mainly by RNAi. Double mutants showed accumulations of LINE-1 retrotransposon transcripts. However, we did not find strong evidence for transcriptional activation and mobilization of retrotransposition competent LINE-1 elements suggesting that while both defense pathways are simultaneously expendable for ovarian oocyte development, yet another transcriptional silencing mechanism prevents mobilization of LINE-1 elements.

Formation of spermatogonia and fertile oocytes in golden hamsters requires piRNAs

“…However, it is unclear whether the dispensability of piRNAs in females is common among mammals. piRNAs target retrotransposons during mouse oogenesis 17 , 18 , but the maternal piRNA pathway is partially redundant with RNA interference (RNAi) 19 . High endogenous RNAi activity specifically evolved in mouse oocytes 20 and seems to be absent in bovine and human oocytes 10 , 21 .…”

Vitamin K in Vertebrates’ Reproduction: Further Puzzling Pieces of Evidence from Teleost Fish Species

“…With the discovery of the key role of non-coding RNAs (ncRNAs) in cell biology, a diverse set of ncRNAs (e.g., micro-RNAs (miRs) and P-element–induced wimpy testis (PIWI)–interacting RNAs (piRs)) involved on vertebrate’s reproduction as well as their corresponding DNA/mRNA target sequences were identified. A key role of piRs in male gametogenesis was clearly evidenced by the male sterility in mice lacking the piR pathway [ 169 ]. Similarly, different miRs have been shown to have great influence on cell mitosis during mammalian gametogenesis (reviewed in [ 170 ]).…”

Golden hamster piRNAs are necessary for early embryonic development and establishment of spermatogonia

“…This suggests impaired repression of FLI-IAPs in Mov10l1 -/oocytes, without global IAP de-repression. In contrast, fertile Mili -/mouse oocytes showed a ~7-fold increase in transcripts matching active IAP subfamilies (18).…”

“…The dispensability of piRNAs in females could be a mouse-specific feature. While piRNAs inhibit retrotransposon expression during mouse oogenesis (15,16), the effective RNA interference (RNAi) pathway, which specifically evolved in mice (17), functionally overlaps with the maternal piRNA pathway (18). Furthermore, mice lack PIWIL3, which binds ~20 nt piRNAs and is expressed in bovine and human oocytes (10,19).…”