小柯机器人

哈佛医学院布拉瓦特尼克研究所Scott Kennedy团队在研究中取得进展。他们揭示了含有聚尿苷（U）和鸟苷（G）尾的RNA（poly（UG）在基因组保护和表观遗传中的功能。2020年5月20日，《自然》在线发表了这一成果。

研究人员发现在自然状态下，秀丽隐杆线虫的核糖核苷酸转移酶RDE-3将pUG尾巴添加到RNA干扰的靶标以及转座子RNA上。含pUG尾的RNA片段具有超过16个完美交替的3'U和G核苷酸作为基因沉默因子。pUG尾巴通过招募依赖于RNA的RNA聚合酶来促进基因沉默，该酶使用含pUG尾的RNA（pUG RNA）作为模板来合成小干扰RNA（siRNA）。

该研究结果表明，在秀丽隐杆线虫种系中，以pUG RNA为模板的siRNA合成和siRNA指导的pUG RNA生物发生周期是双链RNA指导的跨代表观遗传的基础。研究人员推测，这种pUG RNA–siRNA沉默环可以由亲本接种于子代，以防止有害或寄生遗传元件的表达。

据了解，可移动基因元件威胁着所有生物基因组的完整性。RDE-3（也称为MUT-2）是一种核糖核苷酸转移酶，是秀丽隐杆线虫中转座子沉默和RNA干扰所必需的。当与异源表达系统中的RNA束缚在一起时，RDE-3可以在这些RNA的3'末端上添加交替的非模板化U和G核糖核苷酸（poly（UG）或pUG尾巴）长段序列 。

附：英文原文

Title: poly(UG)-tailed RNAs in genome protection and epigenetic inheritance

Author: Aditi Shukla, Jenny Yan, Daniel J. Pagano, Anne E. Dodson, Yuhan Fei, Josh Gorham, J. G. Seidman, Marvin Wickens, Scott Kennedy

Issue&Volume: 2020-05-20

Abstract: Mobile genetic elements threaten genome integrity in all organisms. RDE-3 (also known as MUT-2) is a ribonucleotidyltransferase that is required for transposon silencing and RNA interference in Caenorhabditis elegans1,2,3,4. When tethered to RNAs in heterologous expression systems, RDE-3 can add long stretches of alternating non-templated uridine (U) and guanosine (G) ribonucleotides to the 3′ termini of these RNAs (designated poly(UG) or pUG tails)5. Here we show that, in its natural context in C. elegans, RDE-3 adds pUG tails to targets of RNA interference, as well as to transposon RNAs. RNA fragments attached to pUG tails with more than 16 perfectly alternating 3′ U and G nucleotides become gene-silencing agents. pUG tails promote gene silencing by recruiting RNA-dependent RNA polymerases, which use pUG-tailed RNAs (pUG RNAs) as templates to synthesize small interfering RNAs (siRNAs). Our results show that cycles of pUG RNA-templated siRNA synthesis and siRNA-directed pUG RNA biogenesis underlie double-stranded-RNA-directed transgenerational epigenetic inheritance in the C. elegans germline. We speculate that this pUG RNA–siRNA silencing loop enables parents to inoculate progeny against the expression of unwanted or parasitic genetic elements.

DOI: 10.1038/s41586-020-2323-8

Source: https://www.nature.com/articles/s41586-020-2323-8

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
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