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

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

SUBMITTER: Li G 

PROVIDER: S-EPMC10485882 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

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

Li Guo G   Zhu Xiaoning X   Wang Yihan Y   Ma Hongru H   Wang Yuzhe Y   Wu Hanyu H   Li Xiangyang X   Wang Yiling Y   Gao Jianen J   Chen Xuexin X   Huang Xingxu X   Yao Yuan Y   Hu Xiaoxiang X  

Journal of molecular cell biology 20230601 2

RNA base editing is a promising tool in precise molecular therapy. Currently, there are two widely used RNA base editors, REPAIR and RESCUE. REPAIR only facilitates A-to-I conversions, while RESCUE performs both A-to-I and C-to-U conversions. Thus, RESCUE can generate twice the number of mutations compared to REPAIR. However, transcription-wide impact due to RESCUE-induced off-target single-nucleotide variants (SNVs) is not fully appreciated. Therefore, to determine the off-target effects of RES  ...[more]

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