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N1-methylpseudouridine mRNA modification improves gene overexpression by stopping Prkra-driven widespread protein production shutdown
Updated
Abstract
In zebrafish embryos, double-stranded RNA (dsRNA) by-products from in vitro transcribed messenger RNA (IVT mRNA) can induce cell necrosis and delay maternal-zygotic transition.
- Double-stranded RNA by-products from IVT mRNA are recognized by dsRNA sensors, triggering immune responses.
- These by-products reduce global translation efficiency, impacting early developmental processes.
- (m1Ψ) modification of IVT mRNAs significantly lowers the binding affinity to the dsRNA sensor .
- m1Ψ modification effectively mitigates the harmful effects of dsRNA by-products in early zebrafish embryos.
- The m1Ψ modification reduces dsRNA-induced stress responses in pluripotent cells through a distinct mechanism.
Simplified
Key numbers
20%
Cell Necrosis Rate
Percentage of embryos exhibiting lysis during early development.
5×
Increase in Genome Editing Efficiency
Fold increase in editing efficiency with m1Ψ-modified mRNA compared to unmodified.
mRNA Technology