Transcription-wide impact by RESCUE-induced off-target single-nucleotide variants in mammalian cells  

作　　者：Guo Li Xiaoning Zhu Yihan Wang Hongru Ma Yuzhe Wang Hanyu Wu Xiangyang Li Yiling Wang Jianen Gao Xuexin Chen Xingxu Huang Yuan Yao Xiaoxiang Hu 

机构地区：[1]College of Chemical and Biological Engineering,Zhejiang University,Hangzhou 310027,China [2]ZJU-Hangzhou Global Scientific and Technological Innovation Center,Zhejiang University,Hangzhou 311200,China [3]State Key Laboratory of Agrobiotechnology,College of Biological Sciences,China Agricultural University,Beijing 100193,China [4]National Research Institute for Family Planning,Beijing 100081,China [5]School of Life Science and Technology,ShanghaiTech University,Shanghai 201210,China [6]Institute of Insect Sciences,College of Agriculture and Biotechnology,Zhejiang University,Hangzhou 310058,China [7]Zhejiang Lab,Hangzhou 311121,China

出　　处：《Journal of Molecular Cell Biology》2023年第2期17-28,共12页分子细胞生物学报（英文版）

基　　金：supported by grants from the Ministry of Agriculture of China(2016ZX08009003-006 and 2011ZX08006-001);the National Key Laboratory Open Fund Project(2020SKLAB6-24);the ZJU-Hangzhou Global Scientific and Technological Innovation Center,Zhejiang University(02020200-K02013008);the National Natural Science Foundation of China(32071347).

摘　　要：RNA base editing is a promising tool in precise molecular therapy. Currently, there are two widely used RNA base editors, REPAIRand RESCUE. REPAIR only facilitates A-to-I conversions, while RESCUE performs both A-to-I and C-to-U conversions. Thus, RESCUEcan generate twice the number of mutations compared to REPAIR. However, transcription-wide impact due to RESCUE-induced offtarget single-nucleotide variants (SNVs) is not fully appreciated. Therefore, to determine the off-target effects of RESCUE-mediatedediting, we employed transcription-wide sequencing on cells edited by RESCUE. The SNVs showed different off-target effects onmRNA, circRNA, lncRNA, and miRNA expression patterns and their interacting networks. Our results illustrate the transcriptionwide impact of RESCUE-induced off-target SNVs and highlight the need for careful characterization of the off-target impact by thisediting platform.

关 键 词：transcription-wide off-target SNV RESCUE RNA 

分 类 号：R73[医药卫生—肿瘤]