小柯机器人

美国德克萨斯大学奥斯汀分校David W. Taylor等研究人员合作发现，RNA靶向释放出CRISPR-Cas12a2的无差别核酸酶活性。2023年1月4日，《自然》杂志在线发表了这项成果。

Title: RNA targeting unleashes indiscriminate nuclease activity of CRISPR–Cas12a2

Author: Bravo, Jack P. K., Hallmark, Thomson, Naegle, Bronson, Beisel, Chase L., Jackson, Ryan N., Taylor, David W.

Issue&Volume: 2023-01-04

Abstract: Cas12a2 is a CRISPR-associated nuclease that performs RNA-guided, sequence-nonspecific degradation of single-stranded RNA, single-stranded DNA and double-stranded DNA following recognition of a complementary RNA target, culminating in abortive infection1. Here we report structures of Cas12a2 in binary, ternary and quaternary complexes to reveal a complete activation pathway. Our structures reveal that Cas12a2 is autoinhibited until binding a cognate RNA target, which exposes the RuvC active site within a large, positively charged cleft. Double-stranded DNA substrates are captured through duplex distortion and local melting, stabilized by pairs of ‘aromatic clamp’ residues that are crucial for double-stranded DNA degradation and in vivo immune system function. Our work provides a structural basis for this mechanism of abortive infection to achieve population-level immunity, which can be leveraged to create rational mutants that degrade a spectrum of collateral substrates.

DOI: 10.1038/s41586-022-05560-w

Source: https://www.nature.com/articles/s41586-022-05560-w

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html