{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T15:47:05Z","timestamp":1792252025693,"version":"4.4.0"},"reference-count":78,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"32","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2025,8,8]]},"abstract":"<jats:p>\n            The RNA modification N6-methyladenosine (m\n            <jats:sup>6<\/jats:sup>\n            A) is highly abundant in human brain and implicated in neurological disorders. Profiling m\n            <jats:sup>6<\/jats:sup>\n            A within RNA isoforms is a critical step toward understanding the complex mechanisms that underpin brain function and disease; however, we lack an isoform-level atlas of m\n            <jats:sup>6<\/jats:sup>\n            A sites in the brain. We applied Oxford Nanopore direct RNA sequencing (DRS) to three postmortem human brain regions\u2014prefrontal cortex, caudate nucleus, and cerebellum\u2014to simultaneously investigate the transcriptome and epitranscriptome at the isoform level. We identified 57,000 m\n            <jats:sup>6<\/jats:sup>\n            A sites within 15,000 isoforms, revealing both isoform- and brain region\u2013specific patterning of m\n            <jats:sup>6<\/jats:sup>\n            A modifications. The prefrontal cortex exhibited a distinctive profile of specifically modified isoforms enriched in excitatory neurons and had the highest proportion of unannotated m\n            <jats:sup>6<\/jats:sup>\n            A sites. A population of isoforms were hypermodified and associated with excitatory neurons in all brain regions. Our results demonstrate the utility of isoform-level profiling of RNA modifications and provide insights into brain region specificity with implications for development and disease.\n          <\/jats:p>","DOI":"10.1126\/sciadv.adp0783","type":"journal-article","created":{"date-parts":[[2025,8,8]],"date-time":"2025-08-08T17:58:46Z","timestamp":1754675926000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":17,"title":["Isoform-level profiling of m\n            <sup>6<\/sup>\n            A epitranscriptomic signatures in human brain"],"prefix":"10.1126","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4302-9191","authenticated-orcid":true,"given":"Josie","family":"Gleeson","sequence":"first","affiliation":[{"name":"Department of Anatomy and Physiology, The University of Melbourne, Parkville, VIC, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6606-8196","authenticated-orcid":true,"given":"Sachithrani U.","family":"Madugalle","sequence":"additional","affiliation":[{"name":"Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-0571-9102","authenticated-orcid":true,"given":"Ching Yin","family":"Wan","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Physiology, The University of Melbourne, Parkville, VIC, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0302-5727","authenticated-orcid":true,"given":"Catriona","family":"McLean","sequence":"additional","affiliation":[{"name":"Department of Anatomical Pathology, Alfred Health, Melbourne, VIC, Australia."},{"name":"Victorian Brain Bank, The Florey, Parkville, VIC, 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