Insertion sequences (ISs) are short DNA sequences that can autonomously move within genomes. Although most IS elements show no sequence specificity during transposition, two IS families, IS110 and IS1111, exhibit exceptional target site selectivity. Research from two separate groups has revealed that the sequence specificity of these two families originates from their expression of non-coding RNAs (ncRNAs). These ncRNAs guide sequence-specific DNA integration mediated by recombinases encoded by the IS elements.

Previous studies have shown that a circular DNA intermediate generated by IS1111 family elements can form a promoter at the junction site. Durrant, Perry et al. found that IS110 family members can form such a promoter and drive the expression of an ncRNA, which they called bridge RNA. The bridge RNA contains two internal loops, which recognize the target insertion site and the donor DNA via base-pairing, respectively, thus bringing the two DNA molecules together for recombinase processing. Importantly, both loops can be engineered to reprogram the recombinase to insert several kilobases of DNA into user-defined sites in Escherichia coli cells. The team also showed that bridge RNA can be engineered for use in DNA excision and inversion.

插入序列 (IS) 是可以在基因组内自主移动的短 DNA 序列。尽管大多数 IS 元件在转座过程中不表现出序列特异性，但两个 IS 家族 IS110 和 IS1111 表现出出色的靶位点选择性。两个不同小组的研究表明，这两个家族的序列特异性源于它们非编码 RNA (ncRNA) 的表达。这些 ncRNA 指导由 IS 元件编码的重组酶介导的序列特异性 DNA 整合。

先前的研究表明，IS1111家族元件产生的环状DNA中间体可以在连接位点形成启动子。杜兰特、佩里等人。发现 IS110 家族成员可以形成这样的启动子并驱动 ncRNA 的表达，他们将其称为桥 RNA。桥RNA包含两个内部环，分别通过碱基配对识别目标插入位点和供体DNA，从而将两个DNA分子结合在一起进行重组酶处理。重要的是，两个环都可以被设计为重新编程重组酶，将数千碱基的 DNA 插入大肠杆菌细胞中用户定义的位点。该团队还表明，桥 RNA 可以被设计用于 DNA 切除和倒位。