Genomic rearrangements, encompassing mutational changes in the genome such as insertions, deletions or inversions, are essential for genetic diversity. These rearrangements are typically orchestrated by enzymes that are involved in fundamental DNA repair processes, such as homologous recombination, or in the transposition of foreign genetic material by viruses and mobile genetic elements^1,2. Here we report that IS110 insertion sequences, a family of minimal and autonomous mobile genetic elements, express a structured non-coding RNA that binds specifically to their encoded recombinase. This bridge RNA contains two internal loops encoding nucleotide stretches that base-pair with the target DNA and the donor DNA, which is the IS110 element itself. We demonstrate that the target-binding and donor-binding loops can be independently reprogrammed to direct sequence-specific recombination between two DNA molecules. This modularity enables the insertion of DNA into genomic target sites, as well as programmable DNA excision and inversion. The IS110 bridge recombination system expands the diversity of nucleic-acid-guided systems beyond CRISPR and RNA interference, offering a unified mechanism for the three fundamental DNA rearrangements—insertion, excision and inversion—that are required for genome design.

基因组重排，包括基因组中的突变变化，例如插入、删除或倒位，对于遗传多样性至关重要。这些重排通常由参与基本 DNA 修复过程的酶精心策划，例如同源重组，或病毒和移动遗传元件的外源遗传物质转座 ^1,2 。在这里，我们报道了 IS110 插入序列，这是一个最小的自主移动遗传元件家族，表达一种结构化的非编码 RNA，可与其编码的重组酶特异性结合。该桥 RNA 包含两个内部环，编码与靶 DNA 和供体 DNA（即 IS110 元件本身）碱基配对的核苷酸片段。我们证明靶标结合环和供体结合环可以独立地重新编程以指导两个 DNA 分子之间的序列特异性重组。这种模块化能够将 DNA 插入基因组靶位点，以及可编程的 DNA 切除和倒置。 IS110 桥重组系统扩展了核酸引导系统的多样性，超越了 CRISPR 和 RNA 干扰，为基因组设计所需的三种基本 DNA 重排（插入、切除和倒位）提供了统一的机制。