Partial pairing between the ends of synthetic mRNA controls its expression levels

Partial base pairing between the 5' and 3' untranslated regions of in vitro-transcribed mRNAs promotes circularization and boosts expression levels.

• The presence of a 5' cap and a 3' poly(A) tail is essential for regulating mRNA expression levels.
• Circularization of mRNA is mediated by interactions among specific proteins that bind to the 5' cap and 3' poly(A) tail.
• The expression levels of IVT mRNAs are affected by the lengths of complementary and non-complementary regions in the UTRs.
• A sigmoidal relationship exists between mRNA expression levels and Gibbs free energy changes due to 5'-3' UTR pairing.
• These findings suggest a new approach for designing UTRs in IVT mRNAs to predict their expression based on thermodynamic parameters.

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