Nucleic acids research

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.
Increase in Genome Editing Efficiency
Fold increase in editing efficiency with m1Ψ-modified mRNA compared to unmodified.

Full Text

We can’t show the full text here under this license.

Funding

Competing interests

China patent 202310609693.3 has been authorized to M.S., T.L., and A.J.C. for the application of zebrafish embryos for dsRNA by-product detection.
PubMed

What Lands in Your Inbox Each Week:

  • 📚7 fresh studies
  • 📝plain-language summaries
  • direct links to original studies
  • 🏅top journal indicators
  • 📅weekly delivery
  • 🧘‍♂️always free