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Programmable C-to-U RNA editing using the human APOBEC3A deaminase

文献类型： 外文期刊

作者： Huang, Xinxin 1 ; Lv, Junjun 1 ; Li, Yongqin 1 ; Mao, Shaoshuai 1 ; Li, Zhifang 3 ; Jing, Zhengyu 1 ; Sun, Yidi 4 ; Zhang 1 ;

作者机构： 1.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China

2.Univ Chinese Acad Sci, Beijing, Peoples R China

3.Chinese Acad Agr Sci, Agr Genom Inst Shenzhen, Guangdong Lab Lingnan Modern Agr, Shenzhen Branch,Genome Anal Lab,Minist Agr, Shenzhen, Peoples R China

4.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

5.Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT 06520 USA

关键词： Apobec; programmable; RESCUE; RNA editing; site-directed RNA editing

期刊名称：EMBO JOURNAL （ 影响因子：11.598； 五年影响因子：12.871 ）

ISSN： 0261-4189

年卷期：

页码：

收录情况： SCI

摘要： Programmable RNA cytidine deamination has recently been achieved using a bifunctional editor (RESCUE-S) capable of deaminating both adenine and cysteine. Here, we report the development of "CURE", the first cytidine-specific C-to-U RNA Editor. CURE comprises the cytidine deaminase enzyme APOBEC3A fused to dCas13 and acts in conjunction with unconventional guide RNAs (gRNAs) designed to induce loops at the target sites. Importantly, CURE does not deaminate adenosine, enabling the high-specificity versions of CURE to create fewer missense mutations than RESCUE-S at the off-targets transcriptome-wide. The two editing approaches exhibit overlapping editing motif preferences, with CURE and RESCUE-S being uniquely able to edit UCC and AC motifs, respectively, while they outperform each other at different subsets of the UC targets. Finally, a nuclear-localized version of CURE, but not that of RESCUE-S, can efficiently edit nuclear RNAs. Thus, CURE and RESCUE are distinct in design and complementary in utility.

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