論文種別	原著(症例報告除く)
言語種別	英語
査読の有無	その他(不明)
表題	SARS-CoV-2-Derived RNA Fragment Induces Myocardial Dysfunction via siRNA-like Suppression of Mitochondrial ATP Synthase.
掲載誌名	正式名：International journal of molecular sciences 略　 称：Int J Mol Sci ISSNコード：14220067/14220067
掲載区分	国外
巻・号・頁	26(11),pp.5392
著者・共著者	Shota Nukaga, Rina Fujiwara-Tani, Takuya Mori, Isao Kawahara, Ryoichi Nishida, Yoshihiro Miyagawa, Kei Goto, Hitoshi Ohmori, Kiyomu Fujii, Takamitsu Sasaki, Chie Nakashima, Yi Luo, Shiori Mori, Shingo Kishi, Ruiko Ogata, Hiroki Kuniyasu
発行年月	2025/06
概要	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.
DOI	10.3390/ijms26115392
PMID	40508201