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

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.

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Publication Details

Journal
Genome biology
Published
2026-06-12
DOI
https://doi.org/10.1186/s13059-026-04150-7
Primary Topic
RNA modifications and cancer
Type
article
Field-Weighted Citation Impact
0.00

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article

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

Jiaming Wen, Aolin Li, Chengfang Sun, Jingchao Wei et al.
Genome biology
RNA modifications and cancer
article

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

Jiaming Wen, Aolin Li, Chengfang Sun, Jingchao Wei, Weikai Wang, Qi Huangfu, Yinuo Shu, Xuhong He, Bohan Wang, Ming Cai, Congcong Cao, Letian Shen, J Xu, Yuchen Liu
article en

Abstract

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.

Genome biology
Shenzhen University Health Science Center (CN), Second Affiliated Hospital of Zhejiang University (CN), Shenzhen Second People's Hospital (CN)
National Natural Science Foundation of China, National Key Research and Development Program of China
Good health and well-being
Openalex Percentile: Top 10%
RNA modifications and cancer
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IDMME and IDMDE: inducible CRISPR-dCasRx platforms for spatiotemporal RNA m5C editing — Jiaming Wen, Aolin Li, et al. · Genome biology (2026) | TGRS Research Map | TGRS