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Bridge RNAs direct programmable DNA rearrangements
Nature Biotechnology ( IF 33.1 ) Pub Date : 2024-08-14 , DOI: 10.1038/s41587-024-02365-2
Iris Marchal 1
Affiliation  

The gene editing toolbox is still lacking systems that are capable of precise kilobase-scale DNA modifications. Mobile elements found in bacteria, such as insertion sequences (IS), can orchestrate such large genomic rearrangements, but it has been difficult to reprogram their associated enzymes to target sequence-specific genomic sites. Two papers in Nature now report an RNA-guided recombinase that can be redirected to make diverse and user-specific DNA edits.

Durrant et al. showed that IS110 elements express a noncoding RNA, called bridge RNA, that contains two binding loops that separately recognize the IS110 DNA donor and its genomic insertion target. Notably, they showed that these loops can be engineered to reprogram the recombinase IS621, one member of the IS110 family, to invert, excise or insert large DNA sequences at specific region in the genome of Escherichia coli. Computational analysis identified bridge RNAs in diverse members of the IS110 family, indicating that the bridge recombination mechanism is likely a general feature of IS110 elements.



中文翻译:


桥接RNA可直接编程DNA重排



基因编辑工具箱仍然缺乏能够精确进行千碱基级 DNA 修饰的系统。细菌中发现的移动元件,例如插入序列(IS),可以协调如此大的基因组重排,但很难将其相关酶重新编程以靶向序列特异性基因组位点。 《自然》杂志上的两篇论文现在报道了一种 RNA 引导的重组酶,可以重定向以进行多样化和用户特定的 DNA 编辑。


杜兰特等人。表明IS110元件表达一种非编码RNA,称为桥RNA,它包含两个结合环,分别识别IS110 DNA供体及其基因组插入目标。值得注意的是,他们表明,这些环可以被设计为重新编程重组酶 IS621(IS110 家族的成员之一),以反转、切除或插入大肠杆菌基因组特定区域的大 DNA 序列。计算分析在 IS110 家族的不同成员中发现了桥 RNA,表明桥重组机制可能是 IS110 元件的一般特征。

更新日期:2024-08-14
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