In animals, Argonaute small-RNA pathways scan germline transcripts to silence self-replicating genetic elements. However, little is known about how endogenous gene expression is recognized and licensed. Here, we show that the presence of introns and, by inference, the process of mRNA splicing prevents default Argonaute-mediated silencing in the C. elegans germline. The silencing of intronless genes is initiated independently of the piRNA pathway but nevertheless engages multiple components of the downstream amplification and maintenance mechanisms that mediate transgenerational silencing, including both nuclear and cytoplasmic members of the worm-specific Argonaute gene family (WAGOs). Small RNAs amplified from intronless mRNAs can trans-silence cognate intron-containing genes. Interestingly, a second, small RNA-independent cis-acting mode of silencing also acts on intronless mRNAs. Our findings suggest that cues put in place during mRNA splicing license germline gene expression and provide evidence for a splicing-dependent and dsRNA- and piRNA-independent mechanism that can program Argonaute silencing.

在动物中，Argonaute 小 RNA 通路扫描种系转录本以沉默自我复制的遗传元件。然而，关于如何识别和许可内源基因表达知之甚少。在这里，我们表明内含子的存在以及通过推断，mRNA 剪接过程阻止了秀丽隐杆线虫种系中默认的 Argonaute 介导的沉默。无内含子基因的沉默是独立于 piRNA 途径启动的，但仍涉及介导跨代沉默的下游扩增和维持机制的多个组成部分，包括蠕虫特异性 Argonaute 基因家族 (WAGO) 的核和细胞质成员。从无内含子 mRNA 中扩增的小 RNA 可以反式沉默包含同源内含子的基因。有趣的是，第二种不依赖于小 RNA 的顺式作用模式的沉默也作用于无内含子的 mRNA。我们的研究结果表明，在 mRNA 剪接过程中放置​​的线索允许种系基因表达，并为可以编程 Argonaute 沉默的剪接依赖性和 dsRNA 和 piRNA 独立机制提供证据。