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.
Authors
- Jiaming Wen (ORCID: https://orcid.org/0000-0002-2783-9346)
- Aolin Li (ORCID: https://orcid.org/0000-0003-0988-6787)
- Chengfang Sun (ORCID: https://orcid.org/0000-0003-3511-4123)
- Jingchao Wei (ORCID: https://orcid.org/0000-0002-1037-7990)
- Weikai Wang (ORCID: https://orcid.org/0000-0001-6842-9047)
- Qi Huangfu (ORCID: https://orcid.org/0009-0004-4351-0956)
- Yinuo Shu
- Xuhong He (ORCID: https://orcid.org/0009-0005-5369-7205)
- Bohan Wang (ORCID: https://orcid.org/0000-0003-1065-5011)
- Ming Cai (ORCID: https://orcid.org/0000-0002-2065-0057)
- Congcong Cao (ORCID: https://orcid.org/0000-0003-3895-921X)
- Letian Shen
- J Xu
- Yuchen Liu
Institutions
- Shenzhen University Health Science Center (CN)
- Second Affiliated Hospital of Zhejiang University (CN)
- Shenzhen Second People's Hospital (CN)
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
Funders
- National Natural Science Foundation of China
- National Key Research and Development Program of China