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Activated RNAi does not rescue piRNA pathway deficiency in testes

2024/07/04 by Eliška Táborská, Zuzana Loubalová, Marcos Iuri Roos Kulmann +7 · 1 voice
Agricultural and Biological Sciences · Biochemistry, Genetics and Molecular Biology · #Advanced biosensing and bioanalysis techniques #Biology #Cell biology #Chromosomal and Genetic Variations #Gene #Genetics #Piwi-interacting RNA #RNA #RNA Interference and Gene Delivery #RNA interference

paper · pdf · doi:10.1101/2024.07.04.602103

openalex publication_date 2024/07/04 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/14

Abstract

Abstract RNA interference (RNAi) and PIWI-associated RNAs (piRNA) pathways use small RNAs as sequence-specific guides to repress transposable elements. In mice, the loss of Mili , an essential piRNA pathway factor, causes male sterility associated with mobilization of LINE L1 retrotransposons while female mutants remain fertile. At the same time, mouse oocytes have exceptionally active RNAi thanks to an oocyte-specific variant of RNase III Dicer, which efficiently makes small RNAs from long dsRNA substrates. In oocytes of mice lacking functional MILI and the oocyte-specific Dicer variant, we previously observed that L1 retrotransposons are redundantly targeted by both, RNAi and piRNA pathways. To test whether enhanced RNAi may reduce the Mili mutant phenotype in testes, we used transgenic mice ectopically expressing the oocyte-specific Dicer variant during spermatogenesis. We report here that this genetic modification increases siRNA biogenesis and supports RNAi but is not sufficient to reduce spermatogenic defects caused by the loss of Mili .

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