Small-RNA-mediated transgenerational silencing of histone genes impairs fertility in piRNA mutants.,Nature Cell Biology

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Small-RNA-mediated transgenerational silencing of histone genes impairs fertility in piRNA mutants.
Nature Cell Biology ( IF 17.3 ) Pub Date : 2020-02-03 , DOI: 10.1038/s41556-020-0462-7
Giorgia Barucci _{1,

2} , Eric Cornes ₁ , Meetali Singh ₁ , Blaise Li ₃ , Martino Ugolini _{1,

4} , Aleksei Samolygo _{1,

5} , Celine Didier ₁ , Florent Dingli ₆ , Damarys Loew ₆ , Piergiuseppe Quarato _{1,

2} , Germano Cecere ₁

Affiliation

PIWI-interacting RNAs (piRNAs) promote fertility in many animals. However, whether this is due to their conserved role in repressing repetitive elements (REs) remains unclear. Here, we show that the progressive loss of fertility in Caenorhabditis elegans lacking piRNAs is not caused by derepression of REs or other piRNA targets but, rather, is mediated by epigenetic silencing of all of the replicative histone genes. In the absence of piRNAs, downstream components of the piRNA pathway relocalize from germ granules and piRNA targets to histone mRNAs to synthesize antisense small RNAs (sRNAs) and induce transgenerational silencing. Removal of the downstream components of the piRNA pathway restores histone mRNA expression and fertility in piRNA mutants, and the inheritance of histone sRNAs in wild-type worms adversely affects their fertility for multiple generations. We conclude that sRNA-mediated silencing of histone genes impairs the fertility of piRNA mutants and may serve to maintain piRNAs across evolution.

中文翻译：

小 RNA 介导的组蛋白基因跨代沉默会损害 piRNA 突变体的生育能力。

PIWI 相互作用 RNA (piRNA) 可促进许多动物的生育能力。然而，这是否是由于它们在抑制重复元件（RE）方面的保守作用仍不清楚。在这里，我们发现缺乏 piRNA 的秀丽隐杆线虫生育力的逐渐丧失并不是由 RE 或其他 piRNA 靶标的去抑制引起的，而是由所有复制组蛋白基因的表观遗传沉默介导的。在没有 piRNA 的情况下，piRNA 通路的下游组件从胚芽颗粒重新定位，并且 piRNA 靶向组蛋白 mRNA，以合成反义小 RNA (sRNA) 并诱导跨代沉默。去除 piRNA 途径的下游组件可以恢复 piRNA 突变体中的组蛋白 mRNA 表达和生育力，而野生型线虫中组蛋白 sRNA 的遗传会对它们的多代生育力产生不利影响。我们得出的结论是，sRNA 介导的组蛋白基因沉默会损害 piRNA 突变体的生育能力，并可能有助于在整个进化过程中维持 piRNA。

更新日期：2020-02-03

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