NSUN3-mediated mitochondrial tRNA 5-formylcytidine modification is essential for embryonic development and respiratory complexes in mice.

ABSTRACT: 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 (Nsun3^HKO) mice. Nsun3^HKO heart mitochondria were enlarged and contained fragmented cristae. Nsun3^HKO resulted in enhanced heart contraction and age-associated mild heart enlargement. In the Nsun3^HKO hearts, mitochondrial mRNAs that en

SUBMITTER: Murakami Y 

PROVIDER: S-EPMC10033821 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature