{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T03:35:36Z","timestamp":1792035336695,"version":"4.4.0"},"posted":{"date-parts":[[2026,4,6]]},"group-title":"Pathology","reference-count":66,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T00:00:00Z","timestamp":1775433600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"name":"Texas A&M AgriLife Institute for Advancing Health Through Agriculture (IHA) and the U.S. Department of Agriculture, Agricultural Research Service","award":["NIH"],"award-info":[{"award-number":["NIH"]}]},{"name":"Texas A&M AgriLife Institute for Advancing Health Through Agriculture (IHA) and the U.S. Department of Agriculture, Agricultural Research Service","award":["R01HL145534"],"award-info":[{"award-number":["R01HL145534"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,4,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  The impact of inflammation on heart failure is increasingly recognized; but how cardiomyocyte restrains innate immune activation remains poorly defined, and nor does the role of N\u2076-methyladenosine (m\u2076A) modification in maintaining cardiac immune homeostasis. Here, we demonstrate that cardiomyocyte-specific deletion of the m\u2076A methyltransferase METTL14 triggers myocarditis, dilated cardiomyopathy, and premature lethality. Meanwhile, widespread hypomethylation and upregulation of innate immune and necroptosis-related transcripts in\n                  <jats:italic>Mettl14<\/jats:italic>\n                  -deficient hearts exemplified by IFN-1 and STAT1. Mechanistically, METTL14 deficiency promotes RIPK1 accumulation thereby priming cardiomyocytes for necroptosis and inflammatory cell death. Genetic ablation of IFN-I receptor\n                  <jats:italic>Ifnar1<\/jats:italic>\n                  can largely rescue the processes and improve cardiac function and survival. Furthermore, METTL14 loss disrupts mitochondrial integrity and autophagy\/mitophagy flux, suggesting mitochondrial dysfunction\u2013driven innate immune activation upstream of IFN-I signaling. Collectively, these findings identify METTL14-mediated m\u2076A modification as a critical safeguard against cardiomyocyte-intrinsic IFN-I signaling and necroptosis and establish an epitranscriptomic\u2013innate immune axis that drives inflammatory heart failure.\n                <\/jats:p>","DOI":"10.64898\/2026.04.02.716218","type":"posted-content","created":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T17:45:13Z","timestamp":1775497513000},"source":"Crossref","is-referenced-by-count":1,"title":["METTL14-dependent m\n                  <sup>6<\/sup>\n                  A modification restrains interferon signaling to prevent myocarditis and dilated Cardiomyopathy"],"prefix":"10.64898","author":[{"given":"Yu","family":"Xi","sequence":"first","affiliation":[{"name":"Department of Medical Physiology, Naresh K. Vashisht College of Medicine, Texas A&M University, Bryan, TX 77807"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob","family":"Kuempel","sequence":"additional","affiliation":[{"name":"Department of Medical Physiology, Naresh K. Vashisht College of Medicine, Texas A&M University, Bryan, TX 77807"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sukwon","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Medical Physiology, Naresh K. Vashisht College of Medicine, Texas A&M University, Bryan, TX 77807"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"DeSpain","sequence":"additional","affiliation":[{"name":"Department of Medical Physiology, Naresh K. Vashisht College of Medicine, Texas A&M University, Bryan, TX 77807"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianru","family":"Zhang","sequence":"additional","affiliation":[{"name":"Former address: Department of Biochemistry & Biophysics, Texas A&M University, College Station, TX 77843"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaying","family":"Zhu","sequence":"additional","affiliation":[{"name":"Former address: Department of Biochemistry & Biophysics, Texas A&M University, College Station, TX 77843"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abi","family":"Osborn","sequence":"additional","affiliation":[{"name":"Department of Medical Physiology, Naresh K. Vashisht College of Medicine, Texas A&M University, Bryan, TX 77807"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reed","family":"Rivera","sequence":"additional","affiliation":[{"name":"Department of Medical Physiology, Naresh K. 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