Germ granule dysfunction is a hallmark and mirror of Piwi mutant sterility.

Germ granule dysfunction is a hallmark and mirror of Piwi mutant sterility.
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DOI:
10.1038/s41467-021-21635-0
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发表时间:
2021-03-03
影响因子:
16.6
通讯作者:
Ahmed S
Ahmed S
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Spichal M;Heestand B;Billmyre KK;Frenk S;Mello CC;Ahmed S

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在几个物种中,Piwi/皮尔纳基因组沉默缺陷导致与转座子表达和转座子诱导的基因组不稳定性相关的立即不育。In C.在线虫中,Piwi相关基因(prg-1)的突变和其他皮尔纳缺陷突变体在几代的时间内引起生育力的跨代下降。在这里,我们表明,晚代皮尔纳突变体的不育性与DNA损伤信号传导的增加相关性很差。相反,不育个体始终表现出改变的核周生殖颗粒。我们发现,破坏胚芽颗粒不激活转座子表达,但诱导不育prg-1途径突变体中发现的多种表型。此外,胚芽颗粒成分pgl-1的缺失增强了prg-1突变体不育性。环境恢复不育pgl-1突变体的胚芽粒功能可恢复其育性。我们建议,Piwi突变不育是一种生殖停滞表型,其特征在于由扰动的胚芽颗粒结构和表型复制的胚芽颗粒功能障碍,独立的基因组不稳定性。Piwi缺陷导致不育,并与转座子表达和基因组不稳定性相关。本文作者指出C. Piwi prg-1突变体与转座子诱导的DNA损伤无关,但与生殖颗粒功能障碍相关并被表型模仿。
In several species, Piwi/piRNA genome silencing defects cause immediate sterility that correlates with transposon expression and transposon-induced genomic instability. In C. elegans, mutations in the Piwi-related gene (prg-1) and other piRNA deficient mutants cause a transgenerational decline in fertility over a period of several generations. Here we show that the sterility of late generation piRNA mutants correlates poorly with increases in DNA damage signaling. Instead, sterile individuals consistently exhibit altered perinuclear germ granules. We show that disruption of germ granules does not activate transposon expression but induces multiple phenotypes found in sterile prg-1 pathway mutants. Furthermore, loss of the germ granule component pgl-1 enhances prg-1 mutant infertility. Environmental restoration of germ granule function for sterile pgl-1 mutants restores their fertility. We propose that Piwi mutant sterility is a reproductive arrest phenotype that is characterized by perturbed germ granule structure and is phenocopied by germ granule dysfunction, independent of genomic instability. Piwi deficiency results in sterility and is associated with transposon expression and genomic instability. Here the authors show that sterility of C. elegans Piwi prg-1 mutant is not associated with transposon-induced DNA damage but is associated with and is phenocopied by dysfunction of germ granules.
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