{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T17:50:14Z","timestamp":1782237014690,"version":"3.54.5"},"reference-count":43,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T00:00:00Z","timestamp":1782172800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82201457"],"award-info":[{"award-number":["82201457"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82100471"],"award-info":[{"award-number":["82100471"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Clinical Research Project of Shandong University","award":["2021SDUCRCA007"],"award-info":[{"award-number":["2021SDUCRCA007"]}]},{"DOI":"10.13039\/501100007129","name":"Shandong Provincial Natural Science Foundation","doi-asserted-by":"crossref","award":["ZR2021QH112"],"award-info":[{"award-number":["ZR2021QH112"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Ischemic stroke represents a major global cause of disability and death. Timely recanalization of occluded vessels to salvage the ischemic penumbra is the cornerstone of acute ischemic stroke (AIS) treatment. Nevertheless, the molecular mechanisms driving the transition from salvageable penumbra to infarct core in early AIS remain poorly understood. Recent evidence highlights the role of post-transcriptional methylation, especially N7-methylguanosine (m7G) modification, in stroke pathogenesis. This study aimed to systematically characterize transcriptome-wide m7G methylation changes in the ischemic penumbra during early AIS and to explore their potential functional relevance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed middle cerebral artery occlusion in 8-week-old male BALB\/c mice and applied MeRIP-seq to profile the transcriptome-wide m7G methylome in penumbra tissue. Bioinformatics analyses were conducted to elucidate the functional relevance of m7G-methylated transcripts.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Compared with controls, AIS penumbra exhibited significant alterations in m7G-modified mRNAs. Specifically, upregulated m7G modifications were notably enriched in mRNAs associated with the mitogen-activated protein kinase (MAPK) signaling pathway, whereas downregulated modifications were significantly linked to axon guidance pathways.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study provides the first systematic landscape of m7G methylation in AIS and m7G RNA methylation-related alterations in the MAPK signaling pathway may serve as potential therapeutic targets for stroke intervention.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0352280","type":"journal-article","created":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T17:22:49Z","timestamp":1782235369000},"page":"e0352280","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["A novel m7G RNA methylation-related signature associated with MAPK signaling pathways in acute ischemic stroke"],"prefix":"10.1371","volume":"21","author":[{"given":"Wei-Gang","family":"Gong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian-Wei","family":"Lou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sen","family":"Yin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang-Pu","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-2411-635X","authenticated-orcid":true,"given":"Wei","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,6,23]]},"reference":[{"key":"pone.0352280.ref001","doi-asserted-by":"crossref","first-page":"2820","DOI":"10.1016\/S0140-6736(24)00642-1","volume":"403","author":"NA Hilkens","year":"2024","journal-title":"The Lancet"},{"issue":"5","key":"pone.0352280.ref002","doi-asserted-by":"crossref","first-page":"572","DOI":"10.2174\/1567202619666211231094046","article-title":"Penumbra in acute ischemic stroke","volume":"18","author":"Y Yi","year":"2021","journal-title":"Curr Neurovasc Res"},{"key":"pone.0352280.ref003","doi-asserted-by":"crossref","first-page":"111145","DOI":"10.1016\/j.cellsig.2024.111145","article-title":"WDR4 promotes HCC pathogenesis through N7-methylguanosine by regulating and interacting with METTL1","volume":"118","author":"R Dong","year":"2024","journal-title":"Cell Signal"},{"issue":"1","key":"pone.0352280.ref004","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1186\/s13287-020-01814-4","article-title":"METTL1-mediated m7G methylation maintains pluripotency in human stem cells and limits mesoderm differentiation and vascular development","volume":"11","author":"Y Deng","year":"2020","journal-title":"Stem Cell Res Ther"},{"issue":"1","key":"pone.0352280.ref005","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1186\/s12943-024-02041-8","article-title":"The role of RNA methylation in tumor immunity and its potential in immunotherapy","volume":"23","author":"Y Li","year":"2024","journal-title":"Mol Cancer"},{"issue":"4","key":"pone.0352280.ref006","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1016\/j.jbiotec.2007.11.009","article-title":"Production of yeast tRNA (m(7)G46) methyltransferase (Trm8-Trm82 complex) in a wheat germ cell-free translation system","volume":"133","author":"K Matsumoto","year":"2008","journal-title":"J Biotechnol"},{"issue":"7943","key":"pone.0352280.ref007","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1038\/s41586-022-05565-5","article-title":"Structures and mechanisms of tRNA methylation by METTL1-WDR4","volume":"613","author":"VM Ruiz-Arroyo","year":"2023","journal-title":"Nature"},{"key":"pone.0352280.ref008","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/j.omtn.2023.01.003","article-title":"Internal m7G methylation: A novel epitranscriptomic contributor in brain development and diseases","volume":"31","author":"X Xia","year":"2023","journal-title":"Mol Ther Nucleic Acids"},{"key":"pone.0352280.ref009","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1007\/978-1-0716-2926-0_32","article-title":"Middle cerebral artery occlusion in aged animal model","volume":"2616","author":"GW Goodman","year":"2023","journal-title":"Methods Mol Biol"},{"issue":"4","key":"pone.0352280.ref010","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1203\/00006450-199910000-00006","article-title":"Core and penumbral nitric oxide synthase activity during cerebral ischemia and reperfusion in the rat pup","volume":"46","author":"S Ashwal","year":"1999","journal-title":"Pediatr Res"},{"key":"pone.0352280.ref011","article-title":"RNA-Seq based de novo transcriptome assembly and gene discovery of cistanche deserticola fleshy stem","volume":"10","author":"Y Li","year":"2015","journal-title":"PLoS One"},{"issue":"4","key":"pone.0352280.ref012","doi-asserted-by":"crossref","first-page":"371","DOI":"10.2217\/epi-2019-0260","article-title":"Dynamic N6-methyladenosine RNA methylation in brain and diseases","volume":"12","author":"AM Shafik","year":"2020","journal-title":"Epigenomics"},{"issue":"21","key":"pone.0352280.ref013","doi-asserted-by":"crossref","first-page":"3439","DOI":"10.3390\/cells11213439","article-title":"The DNA methylation in neurological diseases","volume":"11","author":"S Younesian","year":"2022","journal-title":"Cells"},{"issue":"21","key":"pone.0352280.ref014","doi-asserted-by":"crossref","first-page":"11658","DOI":"10.3390\/ijms252111658","article-title":"Epigenetic explorations of neurological disorders, the identification methods, and therapeutic avenues","volume":"25","author":"Z Firdaus","year":"2024","journal-title":"Int J Mol Sci"},{"issue":"12","key":"pone.0352280.ref015","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.3390\/cells13121063","article-title":"Non-Coding RNAs in neurological and neuropsychiatric disorders: unraveling the hidden players in disease pathogenesis","volume":"13","author":"MS Ilieva","year":"2024","journal-title":"Cells"},{"issue":"9","key":"pone.0352280.ref016","doi-asserted-by":"crossref","first-page":"6997","DOI":"10.1007\/s12035-024-04029-3","article-title":"Role of m6A RNA methylation in ischemic stroke","volume":"61","author":"Y Xu","year":"2024","journal-title":"Mol Neurobiol"},{"issue":"3","key":"pone.0352280.ref017","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1080\/14737159.2022.2049246","article-title":"Role of N6-methyladenosine modification in pathogenesis of ischemic stroke","volume":"22","author":"H Chang","year":"2022","journal-title":"Expert Rev Mol Diagn"},{"issue":"11","key":"pone.0352280.ref018","doi-asserted-by":"crossref","first-page":"107777","DOI":"10.1016\/j.celrep.2020.107777","article-title":"Decoding the transcriptional response to ischemic stroke in young and aged mouse braIn","volume":"31","author":"P Androvic","year":"2020","journal-title":"Cell Rep"},{"issue":"6","key":"pone.0352280.ref019","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1007\/s12975-015-0422-x","article-title":"MicroRNA let-7e is a potential circulating biomarker of acute stage ischemic stroke","volume":"6","author":"G Peng","year":"2015","journal-title":"Transl Stroke Res"},{"issue":"11","key":"pone.0352280.ref020","doi-asserted-by":"crossref","first-page":"2000","DOI":"10.1177\/0271678X221116192","article-title":"Epigenetic mechanisms and potential therapeutic targets in stroke","volume":"42","author":"KC Morris-Blanco","year":"2022","journal-title":"J Cereb Blood Flow Metab"},{"issue":"15","key":"pone.0352280.ref021","doi-asserted-by":"crossref","first-page":"7392","DOI":"10.3390\/ijms26157392","article-title":"Human glucose transporters in health and selected neurodegenerative diseases","volume":"26","author":"L Szablewski","year":"2025","journal-title":"Int J Mol Sci"},{"issue":"6","key":"pone.0352280.ref022","doi-asserted-by":"crossref","first-page":"4256","DOI":"10.62347\/JESQ9191","article-title":"Electroacupuncture attenuated cerebral ischemia injury correlated with increased glucose consumption and elevated hippocampal GLUT1\/3 expression","volume":"17","author":"R Xu","year":"2025","journal-title":"Am J Transl Res"},{"issue":"1","key":"pone.0352280.ref023","doi-asserted-by":"crossref","first-page":"4190","DOI":"10.1038\/s41467-025-59400-2","article-title":"Astrocytic GLUT1 deletion in adult mice enhances glucose metabolism and resilience to stroke","volume":"16","author":"L Thieren","year":"2025","journal-title":"Nat Commun"},{"key":"pone.0352280.ref024","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.1161\/STROKEAHA.124.048085","article-title":"Spatial transcriptomics and proteomics profiling after ischemic stroke reperfusion: Insights Into vascular alterations","volume":"56","author":"LMB Hansen","year":"2025","journal-title":"Stroke"},{"issue":"1","key":"pone.0352280.ref025","doi-asserted-by":"crossref","first-page":"8653","DOI":"10.1038\/s41598-025-92714-1","article-title":"Diagnostic value of C-reactive protein\/ albumin ratio and TMTC1 in intracranial atherosclerotic stenosis in patients with acute cerebral infarction","volume":"15","author":"J Mo","year":"2025","journal-title":"Sci Rep"},{"issue":"4","key":"pone.0352280.ref026","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1111\/ahg.12305","article-title":"Significant association of rare variant p.Gly8Ser in cardiac sodium channel \u03b24-subunit SCN4B with atrial fibrillation","volume":"83","author":"H Xiong","year":"2019","journal-title":"Ann Hum Genet"},{"issue":"8","key":"pone.0352280.ref027","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1093\/ehjcvp\/pvad059","article-title":"Bioinformatic platforms for clinical stratification of natural history of atherosclerotic cardiovascular diseases","volume":"9","author":"G Benincasa","year":"2023","journal-title":"Eur Heart J Cardiovasc Pharmacother"},{"key":"pone.0352280.ref028","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.neuroscience.2023.10.014","article-title":"CircAFF2 promotes neuronal cell injury in intracerebral hemorrhage by regulating the miR-488\/CLSTN3 Axis","volume":"535","author":"J Qi","year":"2023","journal-title":"Neuroscience"},{"issue":"7","key":"pone.0352280.ref029","doi-asserted-by":"crossref","first-page":"1635","DOI":"10.1016\/j.cell.2012.05.003","article-title":"Comprehensive analysis of mRNA methylation reveals enrichment in 3\u2019 UTRs and near stop codons","volume":"149","author":"KD Meyer","year":"2012","journal-title":"Cell"},{"key":"pone.0352280.ref030","article-title":"Integrated analysis of the transcriptome-wide m6A methylome in preeclampsia and healthy control placentas","volume":"8","author":"J Wang","year":"2020","journal-title":"PeerJ"},{"key":"pone.0352280.ref031","doi-asserted-by":"crossref","first-page":"177507","DOI":"10.1016\/j.ejphar.2025.177507","article-title":"Netrin-1 binding to UNC5b improves post-stroke neuronal ferroptosis via AMPK-BACH1 pathway","volume":"998","author":"Y Luo","year":"2025","journal-title":"Eur J Pharmacol"},{"issue":"4","key":"pone.0352280.ref032","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1161\/STROKEAHA.118.024631","article-title":"Increased Serum Netrin-1 is associated with improved prognosis of ischemic stroke","volume":"50","author":"D Guo","year":"2019","journal-title":"Stroke"},{"key":"pone.0352280.ref033","first-page":"136","article-title":"UCMSCs-derived exosomal SLIT2 alleviates ischemic stroke through the \u03b2-catenin\/TCF4\/USP20 signaling pathway","author":"R Xiao","year":"2026","journal-title":"Int J Neurosci"},{"issue":"1","key":"pone.0352280.ref034","doi-asserted-by":"crossref","first-page":"1662","DOI":"10.1038\/s42003-025-08988-8","article-title":"Trio and CRMP2 regulate axon branching and Semaphorin3A signaling","volume":"8","author":"E Fingleton","year":"2025","journal-title":"Commun Biol"},{"issue":"11","key":"pone.0352280.ref035","doi-asserted-by":"crossref","first-page":"2060","DOI":"10.3390\/medicina61112060","article-title":"Inflammatory semaphorins in the pathogenesis and prognosis of acute ischemic stroke","volume":"61","author":"E \u00c7i\u00e7ekli","year":"2025","journal-title":"Medicina (Kaunas)"},{"key":"pone.0352280.ref036","doi-asserted-by":"crossref","first-page":"105999","DOI":"10.1016\/j.neubiorev.2024.105999","article-title":"Plexins: Navigating through the neural regulation and brain pathology","volume":"169","author":"A Khan","year":"2025","journal-title":"Neurosci Biobehav Rev"},{"issue":"4","key":"pone.0352280.ref037","doi-asserted-by":"crossref","first-page":"2181","DOI":"10.1096\/fj.201700786RR","article-title":"Sema4D\/PlexinB1 inhibition ameliorates blood-brain barrier damage and improves outcome after stroke in rats","volume":"32","author":"Y-F Zhou","year":"2018","journal-title":"FASEB J"},{"issue":"4","key":"pone.0352280.ref038","doi-asserted-by":"crossref","first-page":"167738","DOI":"10.1016\/j.bbadis.2025.167738","article-title":"Melatonin enhances neurogenesis and neuroplasticity in long-term recovery following cerebral ischemia in mice","volume":"1871","author":"M Beker","year":"2025","journal-title":"Biochim Biophys Acta Mol Basis Dis"},{"issue":"10","key":"pone.0352280.ref039","doi-asserted-by":"crossref","first-page":"1971","DOI":"10.1002\/glia.24232","article-title":"EphA4 regulates white matter remyelination after ischemic stroke through Ephexin-1\/RhoA\/ROCK signaling pathway","volume":"70","author":"C Liu","year":"2022","journal-title":"Glia"},{"issue":"13","key":"pone.0352280.ref040","doi-asserted-by":"crossref","first-page":"6507","DOI":"10.7150\/thno.56367","article-title":"Targeted delivery of neural progenitor cell-derived extracellular vesicles for anti-inflammation after cerebral ischemia","volume":"11","author":"T Tian","year":"2021","journal-title":"Theranostics"},{"issue":"5","key":"pone.0352280.ref041","doi-asserted-by":"crossref","first-page":"1298","DOI":"10.1161\/STROKEAHA.124.045182","article-title":"Genetic insights into hemorrhagic stroke and vascular malformations: Pathogenesis and emerging therapeutic strategies","volume":"56","author":"P Kalailingam","year":"2025","journal-title":"Stroke"},{"issue":"9","key":"pone.0352280.ref042","doi-asserted-by":"crossref","first-page":"1180","DOI":"10.1038\/nm911","article-title":"A peptide inhibitor of c-Jun N-terminal kinase protects against excitotoxicity and cerebral ischemia","volume":"9","author":"T Borsello","year":"2003","journal-title":"Nat Med"},{"issue":"5","key":"pone.0352280.ref043","doi-asserted-by":"crossref","first-page":"2686","DOI":"10.1007\/s12035-023-03706-z","article-title":"Polyphenols targeting MAP kinase signaling pathway in neurological diseases: Understanding molecular mechanisms and therapeutic targets","volume":"61","author":"F Islam","year":"2024","journal-title":"Mol Neurobiol"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0352280","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T17:22:58Z","timestamp":1782235378000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0352280"}},"subtitle":[],"editor":[{"given":"Chandrabose","family":"Selvaraj","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,6,23]]},"references-count":43,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2026,6,23]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0352280","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,23]]}}}