IDMME and IDMDE: inducible CRISPR-dCasRx platforms for spatiotemporal RNA m⁵C editing

RNA 5-methylcytosine (m⁵C) 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 m⁵C methylation (IDMME) and demethylation (IDMDE). These editors enable site-specific, low off-target m⁵C 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 m⁵C 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.