Re-adenylation by TENT5A enhances efficacy of SARS-CoV-2 mRNA vaccines.

ABSTRACT: Despite the widespread use of mRNA vaccines against COVID-19, little is known about the metabolism of therapeutic RNAs. Here we use nanopore sequencing^1-3 to analyse individual therapeutic mRNA molecules, focusing on their poly(A) tails. We show that the Moderna mRNA-1273 vaccine⁴ has a poly(A) tail of around 100 nucleotides, followed by an mΨCmΨAG sequence. In cell lines, mRNA-1273 undergoes rapid degradation initiated by mΨCmΨAG removal, followed by CCR4-NOT-mediated deadenylation. However, in medically relevant preclinical models, particularly in macrophages, mRNA-1273 poly(A) tails are extended to up to 200 nucleotides by the TENT5A poly(A) polymerase^5-7, which is induced by the vaccine. Re-adenylation, which stabilizes target mRNAs, is consistently obs

SUBMITTER: Krawczyk PS 

PROVIDER: S-EPMC12095053 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature