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Peer-reviewedCC BY 4.0RNA (New York, N.Y.)

Cellular signal-responsive m5C editing by an inducible split CRISPR platform

  • Chanjuan Dong1
  • Ying Xu1
  • Kellie Wu1
  • Nathan Mu2
  • Satendra Kumar1
  • Fu-Sen Liang1
  1. 1Department of Chemistry, Case Western Reserve University, Cleveland, Ohio 44106, USA
  2. 2Department of Psychology, Yale University, New Haven, Connecticut 06510, USA
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Abstract

RNA 5-methylcytidine (m5C) modification plays an essential role in regulating RNA metabolism and functions in cellular processes. Tools to achieve temporal and transcript-specific m5C editing for functional studies are still limited. Furthermore, methods enabling m5C editing triggered by specific cellular signals to study m5C functions are currently lacking. Here, we present a temporally and conditionally controlled m5C writing platform engineered through integrating abscisic acid (ABA)-mediated chemically induced proximity with split-dCas13b-NSUN2/NSUN6 technology. This system enables the writing of m5C by reconstituting the split dCas13b-based m5C editing complex at the guide RNA (gRNA)-targeted RNA transcript sites under the control of the inducer ABA. The deposition of m5C is inducible, reversible and selective. The deposited m5C is biologically active and influences the stability of endogenous mRNA transcripts. Moreover, by incorporating ABA prodrugs, the m5C writing can be triggered by signals associated with distinct physiological or disease conditions (e.g., tumor microenvironment and senescence). This conditional m5C editing strategy provides a new programmable tool for studying m5C biology in a context-dependent manner and expands the repertoire of RNA modification editing technologies.

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Cite

BibTeXRIS
BibTeX
@article{dong2026cellular,
  title = {{Cellular signal-responsive m5C editing by an inducible split CRISPR platform}},
  author = {Chanjuan Dong and Ying Xu and Kellie Wu and Nathan Mu and Satendra Kumar and Fu-Sen Liang},
  journal = {RNA (New York, N.Y.)},
  year = {2026},
  month = oct,
  doi = {10.1261/rna.081049.126},
  url = {https://doi.org/10.1261/rna.081049.126},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Cellular signal-responsive m5C editing by an inducible split CRISPR platform
AU  - Chanjuan Dong
AU  - Ying Xu
AU  - Kellie Wu
AU  - Nathan Mu
AU  - Satendra Kumar
AU  - Fu-Sen Liang
PY  - 2026
DA  - 2026/10/16
JO  - RNA (New York, N.Y.)
DO  - 10.1261/rna.081049.126
UR  - https://doi.org/10.1261/rna.081049.126
AB  - RNA 5-methylcytidine (m5C) modification plays an essential role in regulating RNA metabolism and functions in cellular processes. Tools to achieve temporal and transcript-specific m5C editing for functional studies are still limited. Furthermore, methods enabling m5C editing triggered by specific cellular signals to study m5C functions are currently lacking. Here, we present a temporally and conditionally controlled m5C writing platform engineered through integrating abscisic acid (ABA)-mediated chemically induced proximity with split-dCas13b-NSUN2/NSUN6 technology. This system enables the writing of m5C by reconstituting the split dCas13b-based m5C editing complex at the guide RNA (gRNA)-targeted RNA transcript sites under the control of the inducer ABA. The deposition of m5C is inducible, reversible and selective. The deposited m5C is biologically active and influences the stability of endogenous mRNA transcripts. Moreover, by incorporating ABA prodrugs, the m5C writing can be triggered by signals associated with distinct physiological or disease conditions (e.g., tumor microenvironment and senescence). This conditional m5C editing strategy provides a new programmable tool for studying m5C biology in a context-dependent manner and expands the repertoire of RNA modification editing technologies.
SN  - 1355-8382
SN  - 1469-9001
ER  -