Human m(6)A-mRNA and lncRNA epitranscriptomic microarray reveal function of RNA methylation in hemoglobin H-constant spring disease.
Human m(6)A-mRNA and lncRNA epitranscriptomic microarray reveal function of RNA methylation in hemoglobin H-constant spring disease.
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DOI：
10.1038/s41598-021-99867-9
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发表时间：
2021-10-14
影响因子：
4.6
通讯作者：
Pang L
中科院分区：
文献类型：
--
作者：
Ruan H;Yang F;Deng L;Yang D;Zhang X;Li X;Pang L
血红蛋白h -恒定春病（HbH-CS）是非输血型地中海贫血中最常见的类型。有趣的是，相同基因型的地中海贫血的临床表现可能有很大的不同，可能是由于表观遗传调控。在这里，我们使用微阵列技术揭示了m6A在可修饰疾病中的表观遗传调控，并证明了BCL2A1在疾病调控中的作用。在这项研究中，我们发现甲基化酶写入器包括METTL16、WTAP、CBLL1、RBM15B和ZC3H13表现出低表达，而去甲基化酶ALKBH5以及读取器蛋白质包括IGF2BP2和YTHDF3表现出高表达。BCL2A1低甲基化，低表达。我们还发现BCL2A1甲基化水平与IGF2BP2表达呈负相关。此外，ALKBH5和IGF2BP2之间的mrna表达呈正相关。在HbH-CS中，大多数基因是低甲基化的。其中包括BCL2A1，它可能在HbH-CS的红细胞分化和发育过程中发挥重要作用。此外，mRNA-M6A的甲基化状态可能受去甲基化酶ALKBH5通过IGF2BP2调控。
The thalassemia of Hemoglobin H-Constant Spring disease (HbH-CS) is the most common type of Thalassemia in non-transfusion thalassemia. Interestingly, the clinical manifestations of the same genotype of thalassemia can be vastly different, likely due to epigenetic regulation. Here, we used microarray technology to reveal the epigenetic regulation of m6A in modifiable diseases and demonstrated a role of BCL2A1 in disease regulation. In this study, we revealed that methylating enzyme writers including METTL16, WTAP, CBLL1, RBM15B, and ZC3H13 displayed low expression and the demethylating enzyme ALKBH5, along with reader proteins including IGF2BP2 and YTHDF3 exhibited high expression. In addition, BCL2A1 was hypo-methylated and showed low expression. We also revealed that the BCL2A1 methylation level and IGF2BP2 expression were negatively correlated. Additionally, the mRNAs expression between ALKBH5 and IGF2BP2 were positively correlated. In HbH-CS, most genes were hypo-methylated. This included BCL2A1, which may play an important role in the process of red blood cell differentiation and development of HbH-CS. Moreover, the mRNA-M6A methylation status may be regulated by the demethylating enzyme ALKBH5 via IGF2BP2.
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