RNA m6A Modification in Immunocytes and DNA Repair: The Biological Functions and Prospects in Clinical Application.

Mingjie Zhou,Nan Sun,Jieyan Zhang,Wei Liu

doi:10.3389/fcell.2021.794754

Abstract

As the most prevalent internal modification in mRNA, N 6-methyladenosine (m6A) plays broad biological functions via fine-tuning gene expression at the post-transcription level. Such modifications are deposited by methyltransferases (i.e., m6A Writers), removed by demethylases (i.e., m6A Erasers), and recognized by m6A binding proteins (i.e., m6A Readers). The m6A decorations regulate the stability, splicing, translocation, and translation efficiency of mRNAs, and exert crucial effects on proliferation, differentiation, and immunologic functions of immunocytes, such as T lymphocyte, B lymphocyte, dendritic cell (DC), and macrophage. Recent studies have revealed the association of dysregulated m6A modification machinery with various types of diseases, including AIDS, cancer, autoimmune disease, and atherosclerosis. Given the crucial roles of m6A modification in activating immunocytes and promoting DNA repair in cells under physiological or pathological states, targeting dysregulated m6A machinery holds therapeutic potential in clinical application. Here, we summarize the biological functions of m6A machinery in immunocytes and the potential clinical applications via targeting m6A machinery.

Highlights

While RNA modification was first identified in 1970s, it becomes a research focus in recent years
In acute myeloid leukemia (AML), Fat mass and obesity-associated protein (FTO) inhibition can lead to downregulation of leukocyte immunoglobulin-like receptor subfamily B member 4 (LILRB4), render AML cells vulnerable to activated T cells, mainly consists of N6methyladenosine (m6A), Immunocytes and DNA Repair and simultaneously overcome hypomethylating agent (HMA)induced immune evasion
As the most abundant post-transcriptional mRNA modification in mammals, m6A is involved in the occurrence of several diseases

Summary

INTRODUCTION

While RNA modification was first identified in 1970s, it becomes a research focus in recent years. The most momentous breakthrough in this field is the discovery of the m6A machinery involved in m6A modification, including “Writers,” “Erasers” and “Readers,” performing the function of methyltransferase, demethylase, and recognizing the m6A structure, respectively They dynamically regulate the homeostasis of m6A and its functions in cells. In acute myeloid leukemia (AML), FTO inhibition can lead to downregulation of leukocyte immunoglobulin-like receptor subfamily B member 4 (LILRB4), render AML cells vulnerable to activated T cells, FIGURE 2 | m6A-associated proteins in HIV-infected T lymphocytes regulate the expression of HIV mRNA. All the researches above reveal that m6A along with associated protein can alter the stability of mRNA and regulate nuclear export and translation of mRNA, influencing the bioprocess of T cell with different phenotype and promoting the progression of certain diseases

B Lymphocyte

DISCUSSION