Hidden codes in mRNA: Control of gene expression by m(6)A.

Hidden codes in mRNA: Control of gene expression by m(6)A.
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DOI:
10.1016/j.molcel.2022.05.029
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发表时间:
2022-06-16
期刊:
影响因子:
16
通讯作者:
Jaffrey, Samie R.
Jaffrey, Samie R.
中科院分区:
生物学1区
文献类型:
--
作者:
Murakami, Shino;Jaffrey, Samie R.

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mRNA中的信息在很大程度上被认为局限于其核苷酸序列。然而,检测修饰核苷酸的映射技术的出现揭示了mRNA以化学修饰的形式包含额外的信息。最丰富的修饰核苷酸是N6-甲基腺苷(m6 A),腺苷的甲基修饰。虽然早期的研究将m6 A视为动态和组织特异性修饰,但现在清楚的是,含有m6 A的mRNA以及m6 A在这些转录物中的位置在很大程度上是通用的,并且受到基因结构的影响,即,外显子和内含子的大小和位置。m6 A可以影响核过程,如剪接和表观遗传调控,但m6 A对mRNA的主要作用是促进细胞质中的降解。m6 A标志着与某些生物学过程相关的功能相关的mRNA组群,包括细胞分化和细胞命运决定。m6 A也富含其他mRNAs,因此可以影响它们各自的细胞过程和途径。未来的工作将集中在了解m6 A通路是如何调节,以实现控制m6 A的mRNA。在这篇评论中,Murakami et.等人讨论了最近认识到的表转录组调控的概念,重点是N6-甲基腺苷(m6 A),最丰富的内部mRNA修饰。他们描述了m6 A的早期观点,这些观点是如何变化的,并强调了从根本上改变我们对m6 A功能的理解的新兴概念。
Information in mRNA has largely been thought to be confined to its nucleotide sequence. However, the advent of mapping techniques to detect modified nucleotides has revealed that mRNA contains additional information in the form of chemical modifications. The most abundant modified nucleotide is N6-methyladenosine (m6A), a methyl modification of adenosine. Although early studies viewed m6A as a dynamic and tissue-specific modification, it is now clear that the mRNAs that contain m6A and the location of m6A in those transcripts are largely universal, and are influenced by gene architecture, i.e., the size and location of exons and introns. m6A can affect nuclear processes such as splicing and epigenetic regulation, but the major effect of m6A on mRNAs is to promote degradation in the cytoplasm. m6A marks a functionally related cohort of mRNAs linked to certain biological processes, including cell differentiation and cell fate determination. m6A is also enriched in other cohorts of mRNAs and can therefore affect their respective cellular processes and pathways. Future work will focus on understanding how the m6A pathway is regulated to achieve control of m6A-containing mRNAs. In this review, Murakami et. al. discuss the recently recognized concept of epitranscriptomic regulation with a focus on N6-methyladenosine (m6A), the most abundant internal mRNA modification. They describe the early views of m6A, how these views have changed, and highlight emerging concepts that fundamentally change our understanding of how m6A functions.
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