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RNA修饰酶Alkbh8参与小鼠胚胎发育。

RNA-modifying enzyme Alkbh8 is involved in mouse embryonic development.

作者信息

Nakai Manami, Hase Hiroaki, Zhao Yutong, Okawa Katsuya, Honda Kohei, Ikuma Kaori, Kitae Kaori, Tsujikawa Kazutake

机构信息

Laboratory of Molecular and Cellular Physiology, Graduate School of Pharmaceutical Sciences, Osaka University, 1- 6 Yamadaoka, Suita, Osaka 565-0871, Japan.

出版信息

iScience. 2024 Aug 22;27(9):110777. doi: 10.1016/j.isci.2024.110777. eCollection 2024 Sep 20.

Abstract

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 -knockout (KO) mice, the tRNA protein translation efficiency was reduced. Proteome analysis revealed that the factors downregulated in -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.

摘要

RNA在转录后会经历300多种修饰。RNA修饰异常可导致疾病;已有研究表明其与胎儿发育有关。本研究探索了与小鼠胎儿发育相关的RNA修饰。我们使用超高效液相色谱-串联质谱法(UPLC-MS/MS)对小鼠胚胎各阶段(中期II(MII)卵母细胞、原核、2细胞、桑椹胚、囊胚、胚胎第(E)10.5、13.5、16.5和19.5天以及新生小鼠(出生后第[P]0天))中存在的RNA修饰变化进行了定量分析。我们的结果证实许多RNA会经历动态修饰。特别是,5-甲氧基羰基甲基尿苷(mcm5U)修饰具有独特性且在胎儿期增加。在敲除(KO)小鼠中,tRNA的蛋白质翻译效率降低。蛋白质组分析显示,在KO小鼠中下调的因子与红细胞和原卟啉代谢有关。我们的结果表明,ALKBH8与mcm5U共同促进tRNA平衡的变化,这对小鼠正常的红细胞分化和胚胎发生至关重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/82fc/11402254/25b07683f770/fx1.jpg

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