PNLDC1 is essential for piRNA 3' end trimming and transposon silencing during spermatogenesis in mice.

PNLDC1 is essential for piRNA 3' end trimming and transposon silencing during spermatogenesis in mice.
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DOI:
10.1038/s41467-017-00854-4
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发表时间:
2017-10-10
影响因子:
16.6
通讯作者:
Chen C
Chen C
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Ding D;Liu J;Dong K;Midic U;Hess RA;Xie H;Demireva EY;Chen C

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piwi相互作用rna是小的调控rna,在转座子沉默和配子发生调控中起关键作用。成熟的piwi-相互作用RNA的产生需要修剪piwi-相互作用RNA中间体的关键步骤,以获得最佳大小的piwi-相互作用RNA。多聚(A)特异性核糖核酸酶家族死烯化酶PNLDC1与家蚕piwi相互作用的RNA修剪有关。哺乳动物PNLDC1的生理功能尚不清楚。通过使用PNLDC1缺陷小鼠,我们发现PNLDC1是piwi相互作用RNA生物发生、转座子沉默和精子发生所必需的。小鼠Pnldc1突变抑制piwi相互作用RNA修剪,导致未修剪的具有3 '端延伸的piwi相互作用RNA中间体积累,导致睾丸中成熟的piwi相互作用RNA严重减少。Pnldc1突变小鼠表现出LINE1逆转录转座子沉默中断和精子发生缺陷。总之,这些结果确定PNLDC1是一种哺乳动物piwi相互作用的RNA生物发生因子,可以保护种系基因组并确保小鼠正常的精子产生。pirna是在转座子沉默和配子发生中起关键作用的调控rna。在这里,作者提供的证据表明,哺乳动物PNLDC1是piRNA生物发生、转座子沉默和精子发生的调节因子,保护小鼠的种系基因组。
Piwi-interacting RNAs are small regulatory RNAs with key roles in transposon silencing and regulation of gametogenesis. The production of mature piwi-interacting RNAs requires a critical step of trimming piwi-interacting RNA intermediates to achieve optimally sized piwi-interacting RNAs. The poly(A)-specific ribonuclease family deadenylase PNLDC1 is implicated in piwi-interacting RNA trimming in silkworms. The physiological function of PNLDC1 in mammals remains unknown. Using Pnldc1-deficient mice, here we show that PNLDC1 is required for piwi-interacting RNA biogenesis, transposon silencing, and spermatogenesis. Pnldc1 mutation in mice inhibits piwi-interacting RNA trimming and causes accumulation of untrimmed piwi-interacting RNA intermediates with 3′ end extension, leading to severe reduction of mature piwi-interacting RNAs in the testis. Pnldc1 mutant mice exhibit disrupted LINE1 retrotransposon silencing and defect in spermiogenesis. Together, these results define PNLDC1 as a mammalian piwi-interacting RNA biogenesis factor that protects the germline genome and ensures normal sperm production in mice. piRNAs are regulatory RNAs that play a critical role in transposon silencing and gametogenesis. Here, the authors provide evidence that mammalian PNLDC1 is a regulator of piRNA biogenesis, transposon silencing and spermatogenesis, protecting the germline genome in mice.
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