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Disruption of these interactions using a chemical modification of mRNA, 2\u2032-O-methylation (Nm), repressed translation initiation by preventing the preinitiation complex from recognizing start codons. Notably, 2\u2032-O-methylation in upstream AUG and near-cognate codons inhibits upstream translation initiation while enhancing the expression of canonical ORFs. These findings revealed a transcript- and site-specific inhibitory role for 2\u2032-O-methylation in translation initiation, providing novel insights into the mechanisms of start codon selection in human transcriptomes.<\/jats:p>","DOI":"10.1093\/nar\/gkag916","type":"journal-article","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T11:49:10Z","timestamp":1789127350000},"source":"Crossref","is-referenced-by-count":0,"title":["Site-specific inhibition of translation initiation via 2\u2032-O-methylation"],"prefix":"10.1093","volume":"54","author":[{"given":"Adam","family":"Suh","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Feinberg School of Medicine, Northwestern University , Chicago, IL 60611","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Mou","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Feinberg School of Medicine, Northwestern University , Chicago, IL 60611","place":["United States"]},{"name":"Driskill Graduate Program in Life Sciences, Feinberg School of Medicine, Northwestern University , Chicago, IL 60611,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmely A","family":"Patrasso","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Feinberg School of Medicine, Northwestern University , Chicago, IL 60611","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah","family":"Serio","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Feinberg School of Medicine, Northwestern University , Chicago, IL 60611","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Urology, Feinberg School of Medicine, Northwestern University , Chicago, IL 60611 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Urology, Feinberg School of Medicine, Northwestern University , Chicago, IL 60611 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Vasquez","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Feinberg School of Medicine, Northwestern University , Chicago, IL 60611","place":["United States"]},{"name":"Department of Chemical & Biological Engineering, McCormick School of Engineering, Northwestern University , Evanston IL 60208,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Smriti","family":"Sangwan","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Feinberg School of Medicine, Northwestern University , Chicago, IL 60611","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Yi","sequence":"additional","affiliation":[{"name":"Department of Urology, Feinberg School of Medicine, Northwestern University , Chicago, IL 60611 ,","place":["United States"]},{"name":"Robert H. 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