Piwi-interacting RNAs (piRNAs) are RNA effectors with key roles in maintaining genome integrity and promoting fertility in metazoans. In Caenorhabditis elegans loss of piRNAs leads to a transgenerational sterility phenotype. The plethora of piRNAs and their ability to silence transcripts with imperfect complementarity have raised several (non-exclusive) models for the underlying drivers of sterility. Here, we report the extranuclear and transferable nature of the sterility driver, its suppression via mutations disrupting the endogenous RNAi and poly-uridylation machinery, and copy-number amplification at the ribosomal DNA locus. In piRNA-deficient animals, several small interfering RNA (siRNA) populations become increasingly overabundant in the generations preceding loss of germline function, including ribosomal siRNAs (risiRNAs). A concomitant increase in uridylated sense rRNA fragments suggests that poly-uridylation may potentiate RNAi-mediated gene silencing of rRNAs. We conclude that loss of the piRNA machinery allows for unchecked amplification of siRNA populations, originating from abundant highly structured RNAs, to deleterious levels.

Piwi 相互作用 RNA (piRNA) 是 RNA 效应子，在维持基因组完整性和促进后生动物的生育力方面具有关键作用。在秀丽隐杆线虫中piRNA 的缺失导致了跨代不育表型。过多的 piRNA 及其使不完全互补的转录本沉默的能力已经为不育的潜在驱动因素提出了几个（非排他性的）模型。在这里，我们报告了不育驱动的核外和可转移性质，通过破坏内源性 RNAi 和多聚尿苷化机制的突变来抑制它，以及核糖体 DNA 基因座的拷贝数扩增。在 piRNA 缺陷动物中，一些小干扰 RNA (siRNA) 种群在生殖系功能丧失之前的几代中变得越来越多，包括核糖体 siRNA (risiRNA)。尿苷化有义 rRNA 片段的同时增加表明多尿苷化可能增强 RNAi 介导的 rRNA 基因沉默。