Region-specific RNA m(6)A methylation represents a new layer of control in the gene regulatory network in the mouse brain.
Region-specific RNA m(6)A methylation represents a new layer of control in the gene regulatory network in the mouse brain.
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区域特异性 RNA m(6)A 甲基化代表小鼠大脑基因调控网络的新控制层
DOI：
10.1098/rsob.170166
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发表时间：
2017-09
期刊：
影响因子：
5.8
通讯作者：
Tong WM
中科院分区：
文献类型：
--
作者：
Chang M;Lv H;Zhang W;Ma C;He X;Zhao S;Zhang ZW;Zeng YX;Song S;Niu Y;Tong WM
N6-甲基腺苷（m6 A）是mRNA上最丰富的表位转录组标记，在多种生理过程中发挥重要作用。尽管大脑中的m6 A水平相对较高，但其在大脑中的潜在功能在很大程度上仍未被探索。我们使用小鼠大脑进行了全转录组甲基化分析，以描绘其区域特异性甲基化谱。小鼠小脑中的RNA甲基化水平通常高于大脑皮层中的RNA甲基化水平。RNA甲基化的异质性存在于不同的脑区域和不同类型的神经细胞中，包括待甲基化的mRNA、其甲基化水平和甲基化位点选择。常见甲基化和区域特异性甲基化对甲基化位点的选择具有不同的偏好，从而对它们的生物学功能具有不同的影响。此外，脆性X智力低下蛋白（FMRP）靶mRNA的高甲基化水平表明，m6 A甲基化可能用于FMRP在突触中对靶mRNA的选择性识别。总的来说，我们提供了一个区域特异性的RNA m6 A甲基化的地图，并描述了小鼠小脑和大脑皮层中特异性和常见甲基化的独特特征。我们的研究结果表明，RNA m6 A甲基化是一个新发现的元素在区域特异性基因调控网络在小鼠大脑。
N6-methyladenosine (m6A) is the most abundant epitranscriptomic mark found on mRNA and has important roles in various physiological processes. Despite the relatively high m6A levels in the brain, its potential functions in the brain remain largely unexplored. We performed a transcriptome-wide methylation analysis using the mouse brain to depict its region-specific methylation profile. RNA methylation levels in mouse cerebellum are generally higher than those in the cerebral cortex. Heterogeneity of RNA methylation exists across different brain regions and different types of neural cells including the mRNAs to be methylated, their methylation levels and methylation site selection. Common and region-specific methylation have different preferences for methylation site selection and thereby different impacts on their biological functions. In addition, high methylation levels of fragile X mental retardation protein (FMRP) target mRNAs suggest that m6A methylation is likely to be used for selective recognition of target mRNAs by FMRP in the synapse. Overall, we provide a region-specific map of RNA m6A methylation and characterize the distinct features of specific and common methylation in mouse cerebellum and cerebral cortex. Our results imply that RNA m6A methylation is a newly identified element in the region-specific gene regulatory network in the mouse brain.
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