Dev Cell. 2013 Dec 23;27(6):664-71. doi: 10.1016/j.devcel.2013.11.016.
In Caenorhabditis elegans, the Piwi-interacting small RNA (piRNA)-mediated germline surveillance system encodes more than 30,000 unique 21-nucleotide piRNAs, which silence a variety of foreign nucleic acids. What mechanisms allow endogenous germline-expressed transcripts to evade silencing by the piRNA pathway? One likely candidate in a protective mechanism is the Argonaute CSR-1, which interacts with 22G-small RNAs that are antisense to nearly all germline-expressed genes. Here, we use an in vivo RNA tethering assay to demonstrate that the recruitment of CSR-1 to a transcript licenses expression of the transcript, protecting it from piRNA-mediated silencing. Licensing occurs mainly at the level of transcription, as we observe changes in pre-mRNA levels consistent with transcriptional activation when CSR-1 is tethered. Furthermore, the recruitment of CSR-1 to a previously silenced locus transcriptionally activates its expression. Together, these results demonstrate a rare positive role for an endogenous Argonaute pathway in heritably licensing and protecting germline transcripts.
在秀丽隐杆线虫中，Piwi 相互作用的小 RNA（piRNA）介导的生殖系监测系统编码了超过 30000 个独特的 21 个核苷酸 piRNA，这些 piRNA 沉默了多种外源核酸。哪些机制允许内源性生殖系表达的转录本逃避 piRNA 途径的沉默？在保护机制中，一个可能的候选物是 Argonaute CSR-1，它与几乎所有生殖系表达基因的反义 22G-小 RNA 相互作用。在这里，我们使用体内 RNA 系绳测定来证明 CSR-1 对转录物的募集可使转录物的表达获得许可，从而使其免受 piRNA 介导的沉默。许可主要发生在转录水平，因为当 CSR-1 被系绳时，我们观察到与转录激活一致的前体 mRNA 水平的变化。此外，CSR-1 募集到先前沉默的基因座可转录激活其表达。总之，这些结果表明内源性 Argonaute 途径在遗传性许可和保护生殖系转录本方面发挥了罕见的积极作用。
