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内部m7G甲基化:脑发育和疾病中一种新的表观转录组学因素。

Internal m7G methylation: A novel epitranscriptomic contributor in brain development and diseases.

作者信息

Xia Xiaohuan, Wang Yi, Zheng Jialin C

机构信息

Center for Translational Neurodegeneration and Regenerative Therapy, Tongji Hospital affiliated to Tongji University School of Medicine, Shanghai 200072, China.

Shanghai Frontiers Science Center of Nanocatalytic Medicine, Shanghai 200331, China.

出版信息

Mol Ther Nucleic Acids. 2023 Jan 11;31:295-308. doi: 10.1016/j.omtn.2023.01.003. eCollection 2023 Mar 14.

Abstract

In recent years, N7-methylguanosine (m7G) methylation, originally considered as messenger RNA (mRNA) 5' caps modifications, has been identified at defined internal positions within multiple types of RNAs, including transfer RNAs, ribosomal RNAs, miRNA, and mRNAs. Scientists have put substantial efforts to discover m7G methyltransferases and methylated sites in RNAs to unveil the essential roles of m7G modifications in the regulation of gene expression and determine the association of m7G dysregulation in various diseases, including neurological disorders. Here, we review recent findings regarding the distribution, abundance, biogenesis, modifiers, and functions of m7G modifications. We also provide an up-to-date summary of m7G detection and profile mapping techniques, databases for validated and predicted m7G RNA sites, and web servers for m7G methylation prediction. Furthermore, we discuss the pathological roles of METTL1/WDR-driven m7G methylation in neurological disorders. Last, we outline a roadmap for future directions and trends of m7G modification research, particularly in the central nervous system.

摘要

近年来,N7-甲基鸟苷(m7G)甲基化最初被认为是信使核糖核酸(mRNA)5'端帽修饰,现已在多种类型RNA的特定内部位置被发现,包括转运RNA、核糖体RNA、微小RNA(miRNA)和mRNA。科学家们付出了巨大努力来发现RNA中的m7G甲基转移酶和甲基化位点,以揭示m7G修饰在基因表达调控中的重要作用,并确定m7G失调与包括神经疾病在内的各种疾病的关联。在此,我们综述了关于m7G修饰的分布、丰度、生物合成、修饰因子和功能的最新研究发现。我们还提供了m7G检测和图谱绘制技术、经过验证和预测的m7G RNA位点数据库以及m7G甲基化预测网络服务器的最新总结。此外,我们讨论了METTL1/WDR驱动的m7G甲基化在神经疾病中的病理作用。最后,我们概述了m7G修饰研究,特别是在中枢神经系统中的未来方向和趋势路线图。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cbb8/9883147/aa08c2aaedd4/fx1.jpg

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