TIGR-Tas: A family of modular RNA-guided DNA-targeting systems in prokaryotes and their viruses

IF 44.7 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Science Pub Date : 2025-02-27 DOI:10.1126/science.adv9789

Guilhem Faure, Makoto Saito, Max E. Wilkinson, Natalia Quinones-Olvera, Peiyu Xu, Daniel Flam-Shepherd, Stephanie Kim, Nishith Reddy, Shiyou Zhu, Lilia Evgeniou, Eugene V. Koonin, Rhiannon K. Macrae, Feng Zhang

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Abstract

RNA-guided systems provide remarkable versatility, enabling diverse biological functions. Through iterative structural and sequence homology-based mining starting with a guide RNA-interaction domain of Cas9, we identified a family of RNA-guided DNA-targeting proteins in phage and parasitic bacteria. Each system consists of a tandem interspaced guide RNA (TIGR) array and a TIGR-associated (Tas) protein containing a nucleolar protein (Nop) domain, sometimes fused to HNH (TasH)– or RuvC (TasR)–nuclease domains. We show that TIGR arrays are processed into 36-nucleotide RNAs (tigRNAs) that direct sequence-specific DNA binding through a tandem-spacer targeting mechanism. TasR can be reprogrammed for precise DNA cleavage, including in human cells. The structure of TasR reveals striking similarities to box C/D small nucleolar ribonucleoproteins and IS110 RNA-guided transposases, providing insights into the evolution of diverse RNA-guided systems.

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TIGR-Tas：原核生物及其病毒中模块化rna引导的dna靶向系统家族。

rna引导系统提供了显著的多功能性，实现了多种生物功能。从Cas9的引导rna相互作用域开始，通过迭代的结构和序列同源性挖掘，我们在噬菌体和寄生细菌中鉴定了一个rna引导的dna靶向蛋白家族。每个系统由串联间隔引导RNA （TIGR）阵列和含有Nop结构域的TIGR相关（Tas）蛋白组成，有时融合到HNH （TasH）或RuvC （TasR）核酸酶结构域。我们发现TIGR阵列被加工成36-nt rna (tigRNAs)，通过串联间隔器靶向机制直接序列特异性DNA结合。TasR可以被重新编程以进行精确的DNA切割，包括在人类细胞中。TasR的结构显示出与盒C/D snoRNPs和IS110 rna引导转座的惊人相似性，为了解各种rna引导系统的进化提供了见解。

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来源期刊

Science 综合性期刊-综合性期刊

CiteScore

61.10

自引率

0.90%

发文量

审稿时长

2.1 months

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