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Dicer-independent, Ago2-mediated microRNA biogenesis in vertebrates.

机译:不依赖切丁酶的基因,在脊椎动物中由Ago2介导的microRNA生物发生。

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摘要

A canonical biogenesis pathway involving sequential cleavage by the Drosha and Dicer RNAse III enzymes governs the maturation of most animal microRNAs. However, there exist a variety of alternative miRNA biogenesis pathways, most of which bypass Drosha processing. Recently, three groups described for the first time a vertebrate microRNA pathway that bypasses Dicer cleavage. This mechanism was characterized with respect to the highly conserved vertebrate gene mir-451, for which Drosha processing yields a short (42 nucleotide) hairpin that is directly loaded into Ago2, the sole vertebrate "Slicer" Argonaute. Ago2-mediated cleavage of this hairpin yields a 30 nucleotide intermediate, whose 3' end is resected to generate the dominantly cloned ~23 nucleotide mature miR-451. Knowledge of this pathway provides an unprecedented tool with which to express microRNAs and small interfering RNAs in Dicer mutant cells. More generally, the mir-451 backbone constitutes a new platform for gene silencing that complements existing shRNA technology.
机译:规范的生物发生途径涉及Drosha和Dicer RNAse III酶的顺序切割,可控制大多数动物microRNA的成熟。但是,存在多种替代性miRNA生物发生途径,其中大多数绕过Drosha加工。最近,三个研究小组首次描述了绕过Dicer切割的脊椎动物microRNA途径。这种机制针对高度保守的脊椎动物基因mir-451进行了表征,为此,Drosha加工产生了一个短的(42个核苷酸)发夹,该发夹被直接加载到唯一的脊椎动物“ Slicer” Argonaute Ago2中。该发夹的Ago2介导的裂解产生30个核苷酸的中间体,其3'末端被切除以产生显性克隆的〜23个核苷酸的成熟miR-451。对这种途径的了解提供了一种前所未有的工具,可用来在Dicer突变细胞中表达microRNA和小的干扰RNA。更普遍地,mir-451骨架构成了基因沉默的新平台,可补充现有的shRNA技术。

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