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<p>Rewriting RNA information to alter function requires controllable tools to edit RNA sequences within a user-defined region. Here we report a single-strand deaminase-assisted platform for adjustable RNA information manipulation (AIM). AIM is composed of a loop-forming guide RNA bound to an RNA-targeting Cas protein and an evolved TadA. AIM induces a loop, flanked by paired regions, in the target RNA; the loop size can be adjusted to allow conversions of single and multiple bases. We evolve TadA to achieve A-to-I, C-to-U or simultaneous A+C editing in coding and noncoding regions. We apply AIM to suppress the ochre nonsense codon (UAA) in disease-relevant cell and animal models, in which the two As must be simultaneously edited to rewrite the coding information. Moreover, we use AIM to manipulate adjacent phosphorylation sites important for protein function. Collectively, AIM is a versatile platform for manipulating RNA information within user-defined regions, opening additional avenues for functional RNA modulation.</p>

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Single-strand deaminase-assisted editing for functional RNA manipulation

  • 期刊论文

  • 发表日期：

    2026年1月2日

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  • Yuan Zhuang,
  • Qingguo Zhu,
  • Hao Wu,
  • Xiangyue Lin,
  • Yongchang Yan,
  • Puze Geng,
  • Rong Yang,
  • Ruoyu Shen,
  • Yuhao Zhang,
  • Zhixin Lei,
  • Haowei Meng,
  • Aidan Wang,
  • Mingyao Cui,
  • Huifen Xiang,
  • Chengqi Yi

摘要

Rewriting RNA information to alter function requires controllable tools to edit RNA sequences within a user-defined region. Here we report a single-strand deaminase-assisted platform for adjustable RNA information manipulation (AIM). AIM is composed of a loop-forming guide RNA bound to an RNA-targeting Cas protein and an evolved TadA. AIM induces a loop, flanked by paired regions, in the target RNA; the loop size can be adjusted to allow conversions of single and multiple bases. We evolve TadA to achieve A-to-I, C-to-U or simultaneous A+C editing in coding and noncoding regions. We apply AIM to suppress the ochre nonsense codon (UAA) in disease-relevant cell and animal models, in which the two As must be simultaneously edited to rewrite the coding information. Moreover, we use AIM to manipulate adjacent phosphorylation sites important for protein function. Collectively, AIM is a versatile platform for manipulating RNA information within user-defined regions, opening additional avenues for functional RNA modulation.