美国麻省理工学院霍华德休斯医学研究所张锋研究组，发现广泛分布的IS200/605转座子家族编码多种可编程RNA 引导的核酸内切酶。这一研究成果于2021年9月9日发表在国际顶尖学术期刊《科学》上。

他们使用进化分析、RNA-seq 和生化实验，从 IS200/IS605 转座子中重建 CRISPR-Cas9 系统的进化。他们表明 IscB 利用单个非编码 RNA 进行双链 DNA 的 RNA 引导切割，并可用于人类细胞中的基因组编辑。他们还展示了 TnpB 的 RNA 引导的核酸酶活性，TnpB 是另一种 IS200 / 605 转座子编码蛋白，也是 Cas12 核酸内切酶的可能祖先。

这项工作揭示了一类广泛的转座子编码的 RNA 引导的核酸酶，我们将其命名为 OMEGA（Obligate Mobile Element Guided Activity），具有作为生物技术发展的巨大潜力。

据悉，IscB 蛋白是假定的核酸酶，在不同的 IS200/IS605 转座子家族中编码，可能是 RNA 引导的核酸内切酶 Cas9 的祖先，但 IscB 的功能及其与任何 RNA 的相互作用仍未得到表征。

附：英文原文

Title: The widespread IS200/605 transposon family encodes diverse programmable RNA-guided endonucleases

Author: Han Altae-Tran, Soumya Kannan, F. Esra Demircioglu, Rachel Oshiro, Suchita P. Nety, Luke J. McKay, Mensur Dlaki, William P. Inskeep, Kira S. Makarova, Rhiannon K. Macrae, Eugene V. Koonin, Feng Zhang

Issue&Volume: 2021-09-09

Abstract: IscB proteins are putative nucleases encoded in a distinct family of IS200/IS605 transposons and are likely ancestors of the RNA-guided endonuclease Cas9, but the functions of IscB and its interactions with any RNA remain uncharacterized. Using evolutionary analysis, RNA-seq, and biochemical experiments, we reconstruct the evolution of CRISPR-Cas9 systems from IS200/IS605 transposons. We show that IscB utilizes a single non-coding RNA for RNA-guided cleavage of double-stranded DNA and can be harnessed for genome editing in human cells. We also demonstrate the RNA-guided nuclease activity of TnpB, another IS200/605 transposon-encoded protein and the likely ancestor of Cas12 endonucleases. This work reveals a widespread class of transposon-encoded RNA-guided nucleases, which we name OMEGA (Obligate Mobile Element Guided Activity), with strong potential for developing as biotechnologies.

DOI: abj6856

Source: https://www.science.org/doi/10.1126/science.abj6856