RNA-modifying enzyme Alkbh8 is involved in mouse embryonic development

• Published in: iScience 2024-09, Vol.27 (9), p.110777, Article 110777
• Main Authors: Nakai, Manami, Hase, Hiroaki, Zhao, Yutong, Okawa, Katsuya, Honda, Kohei, Ikuma, Kaori, Kitae, Kaori, Tsujikawa, Kazutake
• Format: Article
• Language: English
• Subjects: developmental biology; Embryology; Molecular biology
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2024.110777

RNAs undergo more than 300 modifications after transcription. Aberrations in RNA modifications can lead to diseases; their involvement in fetal development has been suggested. This study explored the RNA modifications related to fetal development in mice. We quantified changes in RNA modifications present in mouse embryos at each stage: Metaphase II (MII) oocyte; pronucleus; 2-cell; morula; blastocyst; embryonic days (E)10.5, 13.5, 16.5, and 19.5; and newborn (post-natal day [P]0) using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Our results confirm that many RNAs undergo dynamic modifications. In particular, 5-methoxycarbonylmethyluridine (mcm5U) modification was distinctive and increased during the fetal period. In Alkbh8-knockout (KO) mice, the tRNA protein translation efficiency was reduced. Proteome analysis revealed that the factors downregulated in Alkbh8-KO mice were associated with red blood cell and protoporphyrin metabolism. Our results suggest that ALKBH8 facilitates changes in tRNA balance in conjunction with mcm5U, which are essential for normal red blood cell differentiation and embryogenesis in mice. [Display omitted] •RNA modification mcm5U and the mcm5U-modifying enzyme Alkbh8 increase after E13.5•In Alkbh8-KO mice, a decrease in body size was observed after E13.5•In Alkbh8-KO E13.5 mice, the cytoplasmic and mitochondrial tRNA balance was altered•Alkbh8 is essential for normal erythrocyte differentiation at E13.5 Molecular biology; Developmental biology; Embryology