Mouse GTSF1 is an essential factor for secondary piRNA biogenesis
Mouse GTSF1 is an essential factor for secondary piRNA biogenesis
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DOI：
10.15252/embr.201642054
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发表时间：
2018-02
期刊：
影响因子：
7.7
通讯作者：
Takuji Yoshimura;Toshiaki Watanabe;Satomi Kuramochi-Miyagawa;N. Takemoto;Yusuke Shiromoto;A. Kudo;M. Kanai-Azuma;F. Tashiro;S. Miyazaki;Ami Katanaya;S. Chuma;J. Miyazaki
中科院分区：
文献类型：
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作者：
Takuji Yoshimura;Toshiaki Watanabe;Satomi Kuramochi-Miyagawa;N. Takemoto;Yusuke Shiromoto;A. Kudo;M. Kanai-Azuma;F. Tashiro;S. Miyazaki;Ami Katanaya;S. Chuma;J. Miyazaki
piRNA 途径是一个 piRNA 引导的逆转录转座子沉默系统，其中包括在次级 piRNA 生物发生中通过 PIWI-piRNA 处理逆转录转座子转录本。尽管有多种蛋白质参与 piRNA 途径，但对于 PIWI-piRNA 切割靶 RNA 至关重要的蛋白质尚未确定。在这里，我们发现 GTSF1（小鼠雄性生殖细胞中逆转录转座子沉默的重要因子）与 MILI 和 MIWI2（在精原细胞中发挥作用的小鼠 PIWI 蛋白）相关。 GTSF1 缺陷会导致次级 piRNA 产生的严重缺陷，次级 piRNA 是由 PIWI-piRNA 的靶 RNA 产生的。此外，在 Gtsf1 突变体中，PIWI-piRNA 的已知靶标 RNA 在切割位点未被切割，并且从该转录本生成次级 piRNA 是有缺陷的。我们的研究结果表明 GTSF1 是 PIWI-piRNA 切割靶 RNA 的关键因素，从而影响精原细胞中次级 piRNA 的生物发生。
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 Gtsf1 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.