{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Krawczyk PS"],"funding":["European Research Council"],"pagination":["984-992"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12095053"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["641(8064)"],"pubmed_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<sup>1-3</sup> to analyse individual therapeutic mRNA molecules, focusing on their poly(A) tails. We show that the Moderna mRNA-1273 vaccine<sup>4</sup> 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<sup>5-7</sup>, which is induced by the vaccine. Re-adenylation, which stabilizes target mRNAs, is consistently obs"],"journal":["Nature"],"pubmed_title":["Re-adenylation by TENT5A enhances efficacy of SARS-CoV-2 mRNA vaccines."],"pmcid":["PMC12095053"],"funding_grant_id":["101097317"],"pubmed_authors":["Affek K","Jelen S","Brouze A","Jemielity J","Tudek A","Nowis D","Golab J","Wesolowska A","Orzel W","Antczak W","Turowski P","Kasztelan K","Guminska N","Spiewla T","Mroczek S","Mazur M","Tarkowski B","Matylla-Kulinska K","Sroka M","Kusio-Kobialka M","Owczarek EP","Gewartowska O","Krawczyk PS","Dziembowski A","Kowalska J"],"additional_accession":[]},"is_claimable":false,"name":"Re-adenylation by TENT5A enhances efficacy of SARS-CoV-2 mRNA vaccines.","description":"Despite the widespread use of mRNA vaccines against COVID-19, little is known about the metabolism of therapeutic RNAs. Here we use nanopore sequencing<sup>1-3</sup> to analyse individual therapeutic mRNA molecules, focusing on their poly(A) tails. We show that the Moderna mRNA-1273 vaccine<sup>4</sup> 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<sup>5-7</sup>, which is induced by the vaccine. Re-adenylation, which stabilizes target mRNAs, is consistently obs","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 May","modification":"2026-06-02T20:45:12.516Z","creation":"2026-04-20T03:10:50.438Z"},"accession":"S-EPMC12095053","cross_references":{"pubmed":["40240603"],"doi":["10.1038/s41586-025-08842-1"]}}