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Disturbed flow is associated with vascular inflammation and focal distribution. Recent studies have revealed the involvement of epigenetic regulation in atherosclerosis progression.\n                    <jats:italic>N<\/jats:italic>\n                    <jats:sup>6<\/jats:sup>\n                    -methyladenosine (m\n                    <jats:sup>6<\/jats:sup>\n                    A) is the most prevalent internal modi\ufb01cation of eukaryotic mRNA, but its function in endothelial atherogenic progression remains unclear. Here, we show that m\n                    <jats:sup>6<\/jats:sup>\n                    A mediates the epidermal growth factor receptor (EGFR) signaling pathway during EC activation to regulate the atherosclerotic process. Oscillatory stress (OS) reduced the expression of methyltransferase like 3 (METTL3), the primary m\n                    <jats:sup>6<\/jats:sup>\n                    A methyltransferase. Through m\n                    <jats:sup>6<\/jats:sup>\n                    A sequencing and functional studies, we determined that m\n                    <jats:sup>6<\/jats:sup>\n                    A mediates the mRNA decay of the vascular pathophysiology gene\n                    <jats:italic>EGFR<\/jats:italic>\n                    which leads to EC dysfunction. m\n                    <jats:sup>6<\/jats:sup>\n                    A modification of the\n                    <jats:italic>EGFR<\/jats:italic>\n                    3\u2019 untranslated regions (3\u2019UTR) accelerated its mRNA degradation. Double mutation of the\n                    <jats:italic>EGFR<\/jats:italic>\n                    3\u2019UTR abolished METTL3-induced luciferase activity. Adenovirus-mediated METTL3 overexpression significantly reduced EGFR activation and endothelial dysfunction in the presence of OS. Furthermore, thrombospondin-1 (TSP-1), an EGFR ligand, was specifically expressed in atheroprone regions without being affected by METTL3. Inhibition of the TSP-1\/EGFR axis by using shRNA and AG1478 significantly ameliorated atherogenesis. Overall, our study revealed that METTL3 alleviates endothelial atherogenic progression through m\n                    <jats:sup>6<\/jats:sup>\n                    A-dependent stabilization of\n                    <jats:italic>EGFR<\/jats:italic>\n                    mRNA, highlighting the important role of RNA transcriptomics in atherosclerosis regulation.\n                  <\/jats:p>","DOI":"10.7554\/elife.69906","type":"journal-article","created":{"date-parts":[[2022,1,10]],"date-time":"2022-01-10T08:01:17Z","timestamp":1641801677000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.69906","source":"Crossref","is-referenced-by-count":37,"title":["RNA N6-methyladenosine modulates endothelial atherogenic responses to disturbed flow in mice"],"prefix":"10.7554","volume":"11","author":[{"given":"Bochuan","family":"Li","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/003sav965","id-type":"ROR","asserted-by":"publisher"}],"name":"Tianjin Key Laboratory of Metabolic 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