Wang Jin, Wang Ke, Liu Wei, Cai Yan, Jin Hua
Prenatal Diagnosis Center, Jinan Maternal and Child Health Care Hospital, Jinan, Shandong Province, PR China.
Psychology Department, Heze Third People's Hospital, Heze, Shandong Province, PR China.
Genomics. 2021 May;113(3):1048-1056. doi: 10.1016/j.ygeno.2021.02.016. Epub 2021 Mar 2.
N6-methyladenosine (m6A) is the most prevalent mRNA modification in mammals. However, m6A modification profiling and its potential role in gestational diabetes mellitus (GDM) have not yet been investigated. In this work, we performed comprehensive m6A analysis in placental tissues from GDM and control patients to elucidate the role of m6A in GDM. An m6A RNA profile identified that m6A levels were strongly decreased in 3'-untranslated regions (UTRs) and coding sequences (CDSs) near stop codons in GDM placenta samples. Among the many methylated mRNAs, MazF-qPCR verified that the m6A levels of the BAMBI 3'-UTR and CDS were significantly decreased in GDM. BAMBI mRNA and protein expression was significantly decreased in GDM, suggesting that m6A plays a key role in regulating gene expression. In addition, it was verified that the m6A levels of GDM related genes (INSR and IRS1) were significantly reduced in GDM. Taken together, our data suggest that down-regulation of m6A both in the 3'-UTR and CDS near stop codons of placental mRNAs is involved in GDM development in Han Chinese women.
N6-甲基腺苷（m6A）是哺乳动物中最普遍的mRNA修饰。然而，m6A修饰谱及其在妊娠期糖尿病（GDM）中的潜在作用尚未得到研究。在这项工作中，我们对GDM患者和对照患者的胎盘组织进行了全面的m6A分析，以阐明m6A在GDM中的作用。m6A RNA谱分析表明，GDM胎盘样本中3'-非翻译区（UTR）和靠近终止密码子的编码序列（CDS）中的m6A水平显著降低。在众多甲基化的mRNA中，MazF-qPCR验证了GDM中BAMBI基因3'-UTR和CDS的m6A水平显著降低。GDM中BAMBI mRNA和蛋白表达显著降低，表明m6A在调节基因表达中起关键作用。此外，还证实GDM相关基因（INSR和IRS1）的m6A水平在GDM中显著降低。综上所述，我们的数据表明，胎盘mRNA靠近终止密码子的3'-UTR和CDS中m6A的下调与中国汉族女性GDM的发生有关。
