J Xu, J Xu, Congcong Cao, Yinuo Shu, Letian Shen, Xuhong He, Qi Huangfu, Chengfang Sun, Weikai Wang, Jingchao Wei, Ming Cai, Bohan Wang, Aolin Li, Yuchen Liu, Jiaming Wen
RNA 5-methylcytosine (m 5 C) is a dynamic epigenetic mark implicated in tumorigenesis, however, existing editors lack spatiotemporal regulation and reversibility. Here, we develop abscisic acid (ABA)-inducible CRISPR-dCasRx systems for programmable m 5 C methylation (IDMME) and demethylation (IDMDE). These editors enable site-specific, low off-target m 5 C modification through ligand-dependent assembly of split effector domains. We further integrate photocaged ABA to achieve light-controlled activation. Application in renal carcinoma models shows that targeted m 5 C editing modulates transcript function and suppresses tumor growth in vitro and in vivo. This platform provides a versatile, spatiotemporally controllable approach for dissecting RNA epigenetic mechanisms and advancing RNA-based therapeutic strategies.