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NSUN3-mediated mitochondrial tRNA 5-formylcytidine modification is essential for embryonic development and respiratory complexes in mice.
Murakami, Yoshitaka; Wei, Fan-Yan; Kawamura, Yoshimi; Horiguchi, Haruki; Kadomatsu, Tsuyoshi; Miyata, Keishi; Miura, Kyoko; Oike, Yuichi; Ando, Yukio; Ueda, Mitsuharu; Tomizawa, Kazuhito; Chujo, Takeshi.
Afiliación
  • Murakami Y; Department of Molecular Physiology, Faculty of Life Sciences, Kumamoto University, Kumamoto, 860-8556, Japan.
  • Wei FY; Department of Neurology, Faculty of Life Sciences, Kumamoto University, Kumamoto, 860-8556, Japan.
  • Kawamura Y; Department of Modomics Biology and Medicine, Institute of Development, Aging and Cancer, Tohoku University, Sendai, 980-8575, Japan.
  • Horiguchi H; Department of Aging and Longevity Research, Faculty of Life Sciences, Kumamoto University, Kumamoto, 860-0811, Japan.
  • Kadomatsu T; Department of Molecular Genetics, Faculty of Life Sciences, Kumamoto University, Kumamoto, 860-8556, Japan.
  • Miyata K; Department of Molecular Genetics, Faculty of Life Sciences, Kumamoto University, Kumamoto, 860-8556, Japan.
  • Miura K; Department of Molecular Genetics, Faculty of Life Sciences, Kumamoto University, Kumamoto, 860-8556, Japan.
  • Oike Y; Department of Aging and Longevity Research, Faculty of Life Sciences, Kumamoto University, Kumamoto, 860-0811, Japan.
  • Ando Y; Center for Metabolic Regulation of Healthy Aging, Kumamoto University, Kumamoto, 860-8556, Japan.
  • Ueda M; Department of Molecular Genetics, Faculty of Life Sciences, Kumamoto University, Kumamoto, 860-8556, Japan.
  • Tomizawa K; Center for Metabolic Regulation of Healthy Aging, Kumamoto University, Kumamoto, 860-8556, Japan.
  • Chujo T; Department of Amyloidosis Research, Faculty of Pharmaceutical Sciences, Nagasaki International University, Sasebo, 859-3298, Japan.
Commun Biol ; 6(1): 307, 2023 03 22.
Article en En | MEDLINE | ID: mdl-36949224
In mammalian mitochondria, translation of the AUA codon is supported by 5-formylcytidine (f5C) modification in the mitochondrial methionine tRNA anticodon. The 5-formylation is initiated by NSUN3 methylase. Human NSUN3 mutations are associated with mitochondrial diseases. Here we show that Nsun3 is essential for embryonic development in mice with whole-body Nsun3 knockout embryos dying between E10.5 and E12.5. To determine the functions of NSUN3 in adult tissue, we generated heart-specific Nsun3 knockout (Nsun3HKO) mice. Nsun3HKO heart mitochondria were enlarged and contained fragmented cristae. Nsun3HKO resulted in enhanced heart contraction and age-associated mild heart enlargement. In the Nsun3HKO hearts, mitochondrial mRNAs that encode respiratory complex subunits were not down regulated, but the enzymatic activities of the respiratory complexes decreased, especially in older mice. Our study emphasizes that mitochondrial tRNA anticodon modification is essential for mammalian embryonic development and shows that tissue-specific loss of a single mitochondrial tRNA modification can induce tissue aberration that worsens in later adulthood.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Anticodón / ARN de Transferencia de Metionina Límite: Adult / Animals / Humans Idioma: En Revista: Commun Biol Año: 2023 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
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XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Anticodón / ARN de Transferencia de Metionina Límite: Adult / Animals / Humans Idioma: En Revista: Commun Biol Año: 2023 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Reino Unido