The N6-Methyladenosine Modification and Its Role in mRNA Metabolism and Gastrointestinal Tract Disease.

Teng Cai,Lawrence Lawer Atteh,Mingzhen Bai,Wenkang Fu,Haidong Ma,Long Gao,Yanyan Lin,Wenbo Meng,Xianzhuo Zhang,Chao Zhang,Chongfei Huang

doi:10.3389/fsurg.2022.819335

Abstract

The N6-methyladenosine (m6A) modification is the most abundant internal modification of messenger RNA (mRNA) in higher eukaryotes. Under the actions of methyltransferase, demethylase and methyl-binding protein, m6A resulting from RNA methylation becomes dynamic and reversible, similar to that from DNA methylation, and this effect allows the generated mRNA to participate in metabolism processes, such as splicing, transport, translation, and degradation. The most common tumors are those found in the gastrointestinal tract, and research on these tumors has flourished since the discovery of m6A. Overall, further analysis of the mechanism of m6A and its role in tumors may contribute to new ideas for the treatment of tumors. m6A also plays an important role in non-tumor diseases of the gastrointestinal tract. This manuscript reviews the current knowledge of m6A-related proteins, mRNA metabolism and their application in gastrointestinal tract disease.

Highlights

Epigenetics refers to heritable changes in gene expression or cell phenotypes that usually occur without alteration of the DNA sequence but rather result in slight or substantial modifications to DNA or RNA
The cells used in this study were not tumor cells, and whether the characteristics of the cells changed after the inhibition of fat mass and obesity-associated protein (FTO) with CHTB is unclear
In vivo and in vitro experiments have fully demonstrated that meclofenamic acid can affect the level of m6A by inhibiting FTO and increase the p53 messenger RNA (mRNA) and protein expression levels, which aggravates the acute kidney injury induced by cisplatin

Summary

Introduction

In CRC, YTHDF2 can increase the m6A modification of GSK3β mRNA, reduce the stability of GSK3β mRNA, and promote its degradation, which induces CRC cell proliferation and tumor progression [68]. Regardless of these limitations, these two studies show that m6A-related proteins and miRNAs can interact and regulate each other and play a role in the occurrence and development of liver cancer. These researchers detected methylases related to m6A and found that the mRNA levels of METTL3 and METTL14 are significantly increased but that WTAP, ALKBH5, and FTO did not exhibit significant changes.

Results

Conclusion