RNA-mediated interference (RNAi) is a conserved mechanism that uses small RNAs (sRNAs) to silence gene expression. In the Caenorhabditis elegans germline, transcripts targeted by sRNAs are used as templates for sRNA amplification to propagate silencing into the next generation. Here we show that RNAi leads to heritable changes in the distribution of nascent and mature transcripts that correlate with two parallel sRNA amplification loops. The first loop, dependent on the nuclear Argonaute HRDE-1, targets nascent transcripts and reduces but does not eliminate productive transcription at the locus. The second loop, dependent on the conserved helicase ZNFX-1, targets mature transcripts and concentrates them in perinuclear condensates. ZNFX-1 interacts with sRNA-targeted transcripts that have acquired poly(UG) tails and is required to sustain pUGylation and robust sRNA amplification in the inheriting generation. By maintaining a pool of transcripts for amplification, ZNFX-1 prevents premature extinction of the RNAi response and extends silencing into the next generation.

RNA 介导的干扰 (RNAi) 是一种保守机制，使用小 RNA (sRNA) 来沉默基因表达。在秀丽隐杆线虫种系中，sRNA 靶向的转录本被用作 sRNA 扩增的模板，以将沉默传播到下一代。在这里，我们表明 RNAi 会导致新生和成熟转录本分布的可遗传变化，这与两个平行的 sRNA 扩增环相关。第一个循环依赖于核 Argonaute HRDE-1，以新生转录本为目标，并减少但不消除该位点的生产性转录。第二个环依赖于保守的解旋酶 ZNFX-1，以成熟转录物为目标并将其集中在核周凝聚物中。 ZNFX-1 与已获得聚 (UG) 尾的 sRNA 靶向转录物相互作用，并且需要在遗传代中维持 pUGylation 和强大的 sRNA 扩增。通过维持用于扩增的转录本池，ZNFX-1 可以防止 RNAi 反应过早消失，并将沉默延伸到下一代。