Lowe David D, Shukla Aditi, Kennedy Scott G
Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.
Whitehead Institute for Biomedical Research, Cambridge, Massachusetts, USA.
bioRxiv. 2025 Jul 9:2025.07.09.663919. doi: 10.1101/2025.07.09.663919.
RNA interference (RNAi) is a component of the innate immune systems of many eukaryotes, including . During RNAi in , the nucleotidyltransferase RDE-3 modifies the 3' termini of mRNAs with polyUG (pUG) tails, which recruit RNA-dependent RNA Polymerase (RdRP) enzymes that drive gene silencing by synthesizing antisense small interfering (si)RNAs. During normal growth and development, RDE-3 pUGylates transposon RNAs to silence transposons and protect genomic integrity. How identifies specific RNAs for pUGylation and whether the pUGylation system is used for other biological purposes is not yet known. Here we show that pUGylation contributes to antiviral immunity in : During infection of with Orsay virus, RDE-3 adds pUG tails to viral RNAs, which converts these RNAs into templates for RdRP-based antiviral siRNA production, thereby limiting viral replication. We present evidence that MUT-15 is critical for viral pUGylation because it interacts with RDE-3 and the NYN domain-containing endonuclease RDE-8, thus bridging the enzymes that cleave and pUGylate viral RNA, ensuring efficient antiviral immunity. We conclude that pUGylation promotes antiviral immunity in and we provide molecular insights into how identifies and neutralizes its internal and external parasitic threats.
RNA干扰（RNAi）是包括……在内的许多真核生物先天免疫系统的一个组成部分。在……的RNAi过程中，核苷酸转移酶RDE-3用聚UG（pUG）尾修饰mRNA的3'末端，这些尾巴招募依赖RNA的RNA聚合酶（RdRP），后者通过合成反义小干扰（si）RNA来驱动基因沉默。在正常生长和发育过程中，RDE-3对转座子RNA进行pUG化修饰，以使转座子沉默并保护基因组完整性。……如何识别用于pUG化修饰的特定RNA以及pUG化修饰系统是否用于其他生物学目的尚不清楚。在这里，我们表明pUG化修饰有助于……的抗病毒免疫：在……被奥赛病毒感染期间，RDE-3给病毒RNA添加pUG尾，这将这些RNA转化为基于RdRP的抗病毒siRNA产生的模板，从而限制病毒复制。我们提供的证据表明，MUT-15对病毒pUG化修饰至关重要，因为它与RDE-3和含NYN结构域的核酸内切酶RDE-8相互作用，从而连接切割和pUG化修饰病毒RNA的酶，确保有效的抗病毒免疫。我们得出结论，pUG化修饰促进……的抗病毒免疫，并且我们提供了关于……如何识别和中和其内部和外部寄生威胁的分子见解。
