Department of Pharmaceutic Sciences, School of Pharmacy, University of Connecticut, Storrs, Connecticut, United States of America.
Department of Pharmacology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China.
PLoS One. 2019 Dec 31;14(12):e0227102. doi: 10.1371/journal.pone.0227102. eCollection 2019.
RNA modifications are recently emerged epigenetic modifications. These diverse RNA modifications have been shown to regulate multiple biological processes, including development. RNA modifications are dynamically controlled by the "writers, erasers, and readers", where RNA modifying proteins are able to add, remove, and recognize specific chemical modification groups on RNAs. However, little is known about the ontogenic expression of these RNA modifying proteins in various organs, such as liver. In the present study, the hepatic mRNA expression of selected RNA modifying proteins involve in m6A, m1A, m5C, hm5C, m7G, and Ψ modifications was analyzed using the RNA-seq technique. Liver samples were collected from male C57BL/6 mice at several ages from prenatal through neonatal, infant, child to young adult. Results showed that most of the RNA modifying proteins were highly expressed in prenatal mouse liver with a dramatic drop at birth. After birth, most of the RNA modifying proteins showed a downregulation trend during liver maturation. Moreover, the RNA modifying proteins that belong to the same enzyme family were expressed at different abundances at the same ages in mouse liver. In conclusion, this study unveils that the mRNA expression of RNA modifying proteins follows specific ontogenic expression patterns in mice liver during maturation. These data indicated that the changes in expression of RNA modifying proteins might have a potential role to regulate gene expression in liver through alteration of RNA modification status.
RNA 修饰是近年来新兴的表观遗传修饰。这些多样化的 RNA 修饰被证明可以调节多种生物学过程,包括发育。RNA 修饰受“writers、erasers 和 readers”动态调控,其中 RNA 修饰蛋白能够在 RNA 上添加、去除和识别特定的化学修饰基团。然而,对于这些 RNA 修饰蛋白在肝脏等各种器官中的胚胎发生表达知之甚少。在本研究中,使用 RNA-seq 技术分析了参与 m6A、m1A、m5C、hm5C、m7G 和 Ψ 修饰的选定 RNA 修饰蛋白在肝脏中的 mRNA 表达。从产前到新生儿、婴儿、儿童到青年期,从雄性 C57BL/6 小鼠中收集了不同年龄的肝脏样本。结果表明,大多数 RNA 修饰蛋白在产前小鼠肝脏中高度表达,出生时急剧下降。出生后,大多数 RNA 修饰蛋白在肝脏成熟过程中表现出下调趋势。此外,属于同一酶家族的 RNA 修饰蛋白在同一时期的小鼠肝脏中以不同的丰度表达。总之,本研究揭示了 RNA 修饰蛋白的 mRNA 表达在小鼠肝脏成熟过程中遵循特定的胚胎发生表达模式。这些数据表明,RNA 修饰蛋白表达的变化可能通过改变 RNA 修饰状态在肝脏中调节基因表达。