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

机译:聚(UG)基因组保护和表观遗传中的RNA

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摘要

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 elegans(1-4). 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.In Caenorhabditis elegans, the ribonucleotidyltransferase RDE-3 adds alternating uridine and guanosine ribonucleotides to the 3 ' termini of RNAs, a key step in RNA interference and thus epigenetic inheritance in the C. elegans germline.
机译:流动遗传元素在所有生物体中威胁到基因组完整性。 RDE-3(也称为mut-2)是一种核糖核苷酰亚烷转移酶,其需要在Caenorhabditis elegans(1-4)中的转座子沉默和RNA干扰所必需的。当在异源表达系统中将RNA旋转到RNA时,RDE-3可以在这些RNA的3'末端添加长长的交替的非模板尿苷(U)和鸟苷(G)核糖核苷酸(指定的聚(UG)或哈巴尾尾)( 5)。在这里,我们表明,在其C.秀丽隐杆线的自然背景下,RDE-3将哈巴尾尾与RNA干扰的靶向添加,以及转座子RNA。附着于哈巴琅尾部的RNA片段,具有超过16个完美交替的3'U和G核苷酸成为基因沉默剂。哈巴狗尾促进通过募集RNA依赖性RNA聚合酶来促进基因沉默,其使用哈巴狗尾部RNA(哈巴)作为模板来合成小干扰RNA(SIRNA)。我们的结果表明,哈巴琅rna-模板siRNA合成的循环和siRNA定向的哈巴格RNA生物生成底层双链RNA定向的转基因的转基因外观遗传遗传。我们推测该帕格RNA-siRNA沉默回路使父母能够接种对不需要的或寄生遗传元件的表达的后代。胶带杆菌,核糖核苷酰亚虫菌酶RDE-3将交替的尿苷和鸟苷核糖核苷酸添加到RNA的3'末端,是RNA的3'末端步骤中的RNA干扰,因此在C. elegans种系中的表观遗传遗传。

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  • 来源
    《Nature》 |2020年第7811期|283-288|共6页
  • 作者单位

    Harvard Med Sch Blavatnik Inst Dept Genet Boston MA 02115 USA;

    Harvard Med Sch Blavatnik Inst Dept Genet Boston MA 02115 USA;

    Harvard Med Sch Blavatnik Inst Dept Genet Boston MA 02115 USA;

    Harvard Med Sch Blavatnik Inst Dept Genet Boston MA 02115 USA;

    Harvard Med Sch Blavatnik Inst Dept Genet Boston MA 02115 USA|Nanjing Agr Univ Coll Agr Nanjing Peoples R China;

    Harvard Med Sch Blavatnik Inst Dept Genet Boston MA 02115 USA;

    Harvard Med Sch Blavatnik Inst Dept Genet Boston MA 02115 USA;

    Univ Wisconsin Dept Biochem 420 Henry Mall Madison WI 53705 USA;

    Harvard Med Sch Blavatnik Inst Dept Genet Boston MA 02115 USA;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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