Talk abstracts
Talk on Friday 02:30-02:45pm submitted by ChanJuan Dong
Cellular signal-responsive m5C editing by an inducible split CRISPR platform
Chanjuan Dong (department of chemistry, Case Western Reserve University), Ying, Xu (department of chemistry, Case Western Reserve University), Kellie, Wu (department of chemistry, Case Western Reserve University), Nathan Mu (Department of Psychology, Yale University), Satendra, Kumar (department of chemistry, Case Western Reserve University)
Abstract:
RNA 5-methylcytidine (mC) modification plays an essential role in regulating RNA metabolism and functions in cellular processes. Tools achieve temporal and transcript-specific mC editing for functional studies are still limited. Furthermore, methods enabling mC editing triggered by specific cellular signals to study mC functions are currently lacking. Here, we present a temporally and conditionally controlled mC writing platform engineered through integrating abscisic acid (ABA)-mediated chemically induced proximity with split-dCas13b-NSUN2/NSUN6 technology. This system enables the writing of mC by reconstituting the split dCas13b-based mC editing complex at the guide RNA (gRNA)-targeted RNA transcript sites under the control of the inducer ABA. The deposition of mC is inducible, reversible and selective. The deposited mC is biologically active and influences the stability of endogenous mRNA transcripts. Moreover, by incorporating ABA prodrugs, the mC writing can be triggered by signals associated with distinct physiological or disease conditions (e.g., tumor microenvironment and senescence). This conditional mC editing strategy provides a new programmable tool for studying mC biology in a context dependent manner and expands the repertoire of RNA modification editing technologies.
References:
Dong, C., Xu, T., Wu, K., Mu, N., Kumar, S., Liang, F. -S.* Cellular signal-responsive m5C editing by an inducible split CRISPR platform. RNA 2026, Accepted.
Keywords: RNA modification, CRISPR, m5C modification