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  3. Rna Folding Nearest Neighbor Parameters Including The Modification 1-methyl-pseudouridine.
  1. Home
  3. Rna Folding Nearest Neighbor Parameters Including The Modification 1-methyl-pseudouridine.

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RNA Folding Nearest Neighbor Parameters Including the Modification 1-Methyl-Pseudouridine.

Elzbieta Kierzek1, Thandolwethu S Shabangu2, Olivia M Hiltke2

  • 1Institute of Bioorganic Chemistry of the Polish Academy of Sciences, Noskowskiego 12/14, 61-704 Poznan, Poland.

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|April 17, 2026

View abstract on PubMed

Summary
This summary is machine-generated.

New nearest neighbor parameters quantify RNA folding stability for sequences containing 1-methyl-pseudouridine. This modification stabilizes RNA folding, improving secondary structure predictions for mRNA therapeutics and natural sequences.

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Area of Science:

  • Biochemistry
  • Molecular Biology
  • Computational Biology

Background:

  • Nearest neighbor analysis is crucial for predicting RNA folding stability.
  • 1-methyl-pseudouridine is a key modification in mRNA vaccines, but its impact on RNA folding was not well understood.

Purpose of the Study:

  • To develop and validate new nearest neighbor parameters for RNA folding that include 1-methyl-pseudouridine.
  • To improve the accuracy of predicting RNA secondary structures with this modified nucleobase.

Main Methods:

  • Derived new nearest neighbor parameters using 208 optical melting experiments.
  • Tested the parameters against an additional 16 optical melting experiments.
  • Incorporated parameters for 1-methyl-pseudouridine-adenine and 1-methyl-pseudouridine-guanine base pairs, as well as loop stability estimations.

Main Results:

  • 1-methyl-pseudouridine substitution generally stabilizes RNA folding, with sequence-dependent effects.
  • The new parameters significantly improved the estimation of tRNA folding ensembles containing 1-methyl-pseudouridine.
  • The developed parameters are integrated into the RNAstructure software.

Conclusions:

  • The new nearest neighbor parameters enable accurate modeling of RNA secondary structures with 1-methyl-pseudouridine.
  • These parameters are vital for understanding and designing mRNA therapeutics and analyzing natural RNA sequences.