{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:21:20Z","timestamp":1760059280099,"version":"build-2065373602"},"reference-count":84,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,6,4]],"date-time":"2025-06-04T00:00:00Z","timestamp":1748995200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001700","name":"MEXT KAKENHI","doi-asserted-by":"publisher","award":["25K14462","25K14487","24K20535","24K14281","23K19900","20K21659"],"award-info":[{"award-number":["25K14462","25K14487","24K20535","24K14281","23K19900","20K21659"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Myocardial injury is a critical determinant of prognosis in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection; however, its underlying mechanisms remain incompletely understood. In this study, we examined the effects of SARS-CoV-2-derived RNA fragments on human cardiomyocytes. We identified a 19-nucleotide sequence within the viral genome that shares complete sequence homology with the human F1F0 ATP synthase subunit alpha gene (ATP5A). This sequence was found to associate with Argonaute 2 (AGO2) and downregulate ATP5A expression via a mechanism analogous to RNA interference. Consequently, oxidative phosphorylation was suppressed in cardiomyocytes, leading to impaired myocardial maturation and the emergence of heart failure-like phenotypes. Notably, exosome-mimetic liposomal delivery of this RNA fragment to cardiomyocytes reproduced the ATP5A-suppressive effect. These findings suggest that SARS-CoV-2-derived RNA fragments may contribute to myocardial injury through the siRNA-like modulation of mitochondrial gene expression. Further validation in animal models and patient-derived materials is warranted.<\/jats:p>","DOI":"10.3390\/ijms26115392","type":"journal-article","created":{"date-parts":[[2025,6,4]],"date-time":"2025-06-04T08:51:04Z","timestamp":1749027064000},"page":"5392","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["SARS-CoV-2-Derived RNA Fragment Induces Myocardial Dysfunction via siRNA-like Suppression of Mitochondrial ATP Synthase"],"prefix":"10.3390","volume":"26","author":[{"given":"Shota","family":"Nukaga","sequence":"first","affiliation":[{"name":"Department of Molecular Pathology, Nara Medical University School of Medicine, Kashihara 634-8521, Japan"},{"name":"Division of Rehabilitation, Hanna Central Hospital, Ikoma 630-0243, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rina","family":"Fujiwara-Tani","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology, Nara 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