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Programmable RNA editing with compact CRISPR-Cas13 systems from uncultivated microbes

文献类型：期刊论文

作者Xu, Chunlong7; Zhou, Yingsi7; Xiao, Qingquan7,8; He, Bingbing7,8; Geng, Guannan7; Wang, Zikang7; Cao, Birong1,8; Dong, Xue7; Bai, Weiya2; Wang, Yifan7
刊名NATURE METHODS
出版日期2021-05-03
页码29
ISSN号1548-7091
DOI10.1038/s41592-021-01124-4
通讯作者Zhou, Yingsi(yszhou@ion.ac.cn) ; Lai, Jinsheng(jlai@cau.edu.cn) ; Yang, Hui(huiyang@ion.ac.cn)
英文摘要Competitive coevolution between microbes and viruses has led to the diversification of CRISPR-Cas defense systems against infectious agents. By analyzing metagenomic terabase datasets, we identified two compact families (775 to 803 amino acids (aa)) of CRISPR-Cas ribonucleases from hypersaline samples, named Cas13X and Cas13Y. We engineered Cas13X.1 (775 aa) for RNA interference experiments in mammalian cell lines. We found Cas13X.1 could tolerate single-nucleotide mismatches in RNA recognition, facilitating prophylactic RNA virus inhibition. Moreover, a minimal RNA base editor, composed of engineered deaminase (385 aa) and truncated Cas13X.1 (445 aa), exhibited robust editing efficiency and high specificity to induce RNA base conversions. Our results suggest that there exist untapped bacterial defense systems in natural microbes that can function efficiently in mammalian cells, and thus potentially are useful for RNA-editing-based research. This work describes the identification of Cas13 proteins from two families by mining public metagenomic data. The newly identified Cas13X.1 shows efficient target knockdown and can be used to degrade SARS-CoV-2 and H1N1 genomes. In addition, the truncated Cas13X.1 offers an advantage in generating mini-RNA base editors.
WOS关键词EVOLUTIONARY CLASSIFICATION ; DISCOVERY ; DATABASE
资助项目Chinese Academy of Sciences[ZDBS-LY-SM001] ; R&D Program of China[2017YFC1001300] ; R&D Program of China[2018YFC2000100] ; CAS Strategic Priority Research Program[XDB32060000] ; National Natural Science Foundation of China[31871502] ; National Natural Science Foundation of China[31925016] ; National Natural Science Foundation of China[91957122] ; National Natural Science Foundation of China[31901047] ; National Natural Science Foundation of China[82021001] ; Shanghai Municipal Science and Technology Major Project[2018SHZDZX05] ; Shanghai City Committee of Science and Technology Project[18411953700] ; Shanghai City Committee of Science and Technology Project[18JC1410100] ; Shanghai City Committee of Science and Technology Project[19XD1424400] ; Shanghai City Committee of Science and Technology Project[19YF1455100] ; International Partnership Program of Chinese Academy of Sciences[153D31KYSB20170059]
WOS研究方向Biochemistry & Molecular Biology
语种英语
WOS记录号WOS:000646531300002
出版者NATURE RESEARCH
源URL[http://119.78.100.183/handle/2S10ELR8/296693]  
专题中国科学院上海药物研究所
通讯作者Zhou, Yingsi; Lai, Jinsheng; Yang, Hui
作者单位1.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai, Peoples R China
2.Huigene Therapeut Inc, Shanghai, Peoples R China
3.Tianjin Med Univ, Sch Basic Med Sci, Dept Pathogen Biol, Tianjin, Peoples R China
4.Chinese Acad Agr Sci, Agr Genome Inst Shenzhen, Ctr Anim Genom, Shenzhen, Peoples R China
5.China Agr Univ, Dept Plant Genet & Breeding, State Key Lab Agrobiotechnol, Beijing, Peoples R China
6.Fudan Univ, Shanghai Publ Hlth Clin Ctr, Shanghai, Peoples R China
7.Chinese Acad Sci, Shanghai Res Ctr Brain Sci & Brain Inspired Intel, Shanghai Inst Biol Sci,CAS Ctr Excellence Brain S, Inst Neurosci,State Key Lab Neurosci,Key Lab Prim, Shanghai, Peoples R China
8.Univ Chinese Acad Sci, Coll Life Sci, Beijing, Peoples R China
9.China Agr Univ, Dept Plant Genet & Breeding, Natl Maize Improvement Ctr, Beijing, Peoples R China
推荐引用方式
GB/T 7714		 Xu, Chunlong,Zhou, Yingsi,Xiao, Qingquan,et al. Programmable RNA editing with compact CRISPR-Cas13 systems from uncultivated microbes[J]. NATURE METHODS,2021:29.
APA Xu, Chunlong.,Zhou, Yingsi.,Xiao, Qingquan.,He, Bingbing.,Geng, Guannan.,...&Yang, Hui.(2021).Programmable RNA editing with compact CRISPR-Cas13 systems from uncultivated microbes.NATURE METHODS,29.
MLA Xu, Chunlong,et al."Programmable RNA editing with compact CRISPR-Cas13 systems from uncultivated microbes".NATURE METHODS (2021):29.

入库方式： OAI收割

来源：上海药物研究所

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