N(1)-methylpseudouridylation of mRNA causes +1 ribosomal frameshifting. (10.1038/s41586-023-06800-3 [doi])

These scientists were studying a type of medicine called mRNA vaccines. These vaccines are used to fight against diseases in our bodies. The scientists wanted to see if they could make these vaccines even better.

To do this, they made some changes to the mRNA molecules that are used in the vaccines. They added something called N(1)-methylpseudouridine to the mRNA. They wanted to see how this change affected the way the mRNA is translated into proteins in our cells.

They found that when they added N(1)-methylpseudouridine to the mRNA, it caused a small mistake in the way the proteins were made. It made the proteins shift by one position, like when you accidentally move one letter in a word to the left or right.

The scientists also tested the vaccines on mice and humans. They found that when the mRNA was translated with this small mistake, it caused our immune system to respond differently. This means that the vaccines might not work as well as they should.

However, the scientists also discovered a way to fix this problem. They found that if they changed some specific parts of the mRNA, they could prevent the mistake from happening. This means they can make the vaccines better by making sure the proteins are made correctly.

Overall, this study helped the scientists understand how these changes to the mRNA can affect the vaccines. It showed that while the vaccines we have now are safe, we need to be careful and make sure to optimize the mRNA sequences in the future to avoid any potential problems.

Mulroney TE., Poyry T., Yam-Puc JC., Rust M., Harvey RF., Kalmar L., Horner E., Booth L., Ferreira AP., Stoneley M., Sawarkar R., Mentzer AJ., Lilley KS., Smales CM., von der Haar T., Turtle L., Dunachie S., Klenerman P., Thaventhiran JED., Willis AE. N(1)-methylpseudouridylation of mRNA causes +1 ribosomal frameshifting. Nature. 2024 Jan;625(7993):189-194. doi: 10.1038/s41586-023-06800-3. Epub 2023 Dec 6.