小鼠 GTSF1 是次级 piRNA 生物发生的必需因素。
Mouse GTSF1 is an essential factor for secondary piRNA biogenesis.
机构信息
Laboratory of Reproductive Engineering, The Institute of Experimental Animal Sciences, Osaka University Medical School, Suita, Osaka, Japan.
Division of Stem Cell Regulation Research, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
出版信息
EMBO Rep. 2018 Apr;19(4). doi: 10.15252/embr.201642054. Epub 2018 Feb 7.
The piRNA pathway is a piRNA-guided retrotransposon silencing system which includes processing of retrotransposon transcripts by PIWI-piRNAs in secondary piRNA biogenesis. Although several proteins participate in the piRNA pathway, the ones crucial for the cleavage of target RNAs by PIWI-piRNAs have not been identified. Here, we show that GTSF1, an essential factor for retrotransposon silencing in male germ cells in mice, associates with both MILI and MIWI2, mouse PIWI proteins that function in prospermatogonia. GTSF1 deficiency leads to a severe defect in the production of secondary piRNAs, which are generated from target RNAs of PIWI-piRNAs. Furthermore, in mutants, a known target RNA of PIWI-piRNAs is left unsliced at the cleavage site, and the generation of secondary piRNAs from this transcript is defective. Our findings indicate that GTSF1 is a crucial factor for the slicing of target RNAs by PIWI-piRNAs and thus affects secondary piRNA biogenesis in prospermatogonia.
piRNA 通路是一个由 piRNA 指导的逆转录转座子沉默系统，包括在次级 piRNA 生物发生中通过 PIWI-piRNAs 对逆转录转座子转录本的加工。虽然有几种蛋白质参与 piRNA 通路，但尚未鉴定出对 PIWI-piRNAs 切割靶 RNA 至关重要的蛋白质。在这里，我们表明 GTSF1 是小鼠生殖细胞中逆转录转座子沉默的必需因子，与 MILI 和 MIWI2 相关，MILI 和 MIWI2 是在精原细胞中发挥作用的小鼠 PIWI 蛋白。GTSF1 缺陷导致次级 piRNA 的产生严重缺陷，这些 piRNA 是由 PIWI-piRNAs 的靶 RNA 产生的。此外，在 突变体中，PIWI-piRNAs 的一个已知靶 RNA 在切割位点未被切割，并且该转录本的次级 piRNA 的产生有缺陷。我们的研究结果表明，GTSF1 是 PIWI-piRNAs 切割靶 RNA 的关键因素，因此影响精原细胞中次级 piRNA 的生物发生。
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