美国加州大学伯克利分校Patrick D. Hsu团队发现，桥RNA引导靶标DNA和供体DNA的可编程重组。这一研究成果发表在2024年6月26日出版的国际学术期刊《自然》上。

研究人员报告了IS110插入序列，这是一个最小和自主的移动遗传元件家族，它表达一种结构化的非编码RNA，这种RNA与它们编码的重组酶特异性结合。这种桥RNA包含两个内部环路，编码与目标DNA和供体DNA（即IS110基因元件本身）碱基配对的核苷酸链。研究人员证明，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。

这种模块化特性使DNA能够插入基因组靶标位点，以及可编程的DNA切除和反转。IS110桥重组系统扩展了CRISPR和RNA干扰之外的核酸引导系统的多样性，为基因组设计所需的三种基本DNA重排（插入、切除和反转）提供了统一的机制。

据悉，基因组重排包括基因组中的突变，如插入、缺失或倒位，对遗传多样性至关重要。这些重排通常是由参与DNA基本修复过程（如同源重组）或参与病毒和移动遗传因子转位外来遗传物质的酶来协调的。

附：英文原文

Title: Bridge RNAs direct programmable recombination of target and donor DNA

Author: Durrant, Matthew G., Perry, Nicholas T., Pai, James J., Jangid, Aditya R., Athukoralage, Januka S., Hiraizumi, Masahiro, McSpedon, John P., Pawluk, April, Nishimasu, Hiroshi, Konermann, Silvana, Hsu, Patrick D.

Issue&Volume: 2024-06-26

Abstract: 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 elements1,2. 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.

DOI: 10.1038/s41586-024-07552-4

Source: https://www.nature.com/articles/s41586-024-07552-4