Abstract

N6-Methyladenosine (m6A), the most abundant internal modification associated with eukaryotic mRNAs, has emerged as a dynamic regulatory mechanism controlling the expression of genes involved in many physiological activities by affecting various steps of mRNA metabolism, including splicing, export, translation, and stability. Here, we review the general role of m6A, highlighting recent advances related to the three major types enzymes that determine the level of m6A modification (i.e., writers, erasers, and readers) and the regulatory mechanism by which m6A influences multiple stages of RNA metabolism. This review clarifies the close connection and interaction between m6A modification and nuclear gene expression, and provides key background information for further studies of its roles in numerous physiological and pathophysiological processes. Among them, perhaps the most eye-catching process is tumorigenesis. Clarifying the molecular mechanism of tumorigenesis, development and metastasis in various tissues of the human body is conducive to curbing out-of-control cell activities from the root and providing a new strategy for human beings to defeat tumors.

Highlights

  • There are more than 170 chemical modifications in RNA

  • We found that catalytically inactive Methyltransferase-like 3 (METTL3) interacts with eukaryotic translation initiation factor 3 subunit h to enhance translation when tethered to reporter mRNA at m6A sites close to the stop codon [43]. eIf3 directly binds to the m6A site in the 5ʹ untranslated regions (UTRs) to drive translation [44]

  • MRNA translation At the molecular level, the mechanism by which m6A modification improves the translation efficiency is mainly dependent on the binding of reader proteins to protein factors required in the translation process, and m6A modifications located in different RNA regions exert effects by various modes of action

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Summary

Introduction

There are more than 170 chemical modifications in RNA. Among these, N6-Methyladenosine (m6A) is methylation at the N6 position of adenosine and has been considered as the most abundant and conserved internal transcriptional modification within eukaryotic RNAs. The wide distribution of regulatory subunits of m6a readers in cells and variety of biological functions reveals an additional regulatory layer of the m6A pathway and m6A recognition: in addition to various protein, other types of RNA can participate in the identification of m6A modification on mRNA.

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Conclusion

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