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

Abstract

As the most prevalent internal modification in mRNA, N6-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.

m6A ‘writer’ KIAA1429 regulates the proliferation and migration of endothelial cells in atherosclerosis

“…In atherosclerosis (AS), the activity of vascular endothelial cells could reflect cells’ metabolism and proliferation [ 17 – 19 ]. AS is a life-threatening vascular disease, and m 6 A modification level is dysregulated in its pathophysiologic processes of AS [ 20 , 21 ]. Here, we found that m 6 A writer KIAA1429 upregulated in ox-LDL-induced HUVECs.…”

N6-methyladenosine modified AFAP1-AS1 accelerates hepatocellular carcinoma proliferation and migration via miR-195-5p/KIAA1429 feedback loop

“…Thus, these evidences suggest the critical roles of lncRNA AFAP1-AS1 in human cancer. KIAA1429, acts as an m 6 A methyltransferase ('writer'), was found to be up-regulated in the HCC tissue samples and cells [16,17]. And this is a very interesting point that KIAA1429 bound with the m 6 A methylated site in AFAP1-AS1 genomic sequences, and KIAA1429 promotes the RNA stability of AFAP1-AS1 upon Act D administration.…”

The effects of RNA methylation on immune cells development and function

“…Therefore, experts believe that inhibiting m6A might boost the pluripotency of stem cells, implying the potential of m6A to direct immunocyte differentiation. In recent years, there has been a growing body of evidence that in the human immune system, m6A plays a role in antigen recognition and presentation as well as in innate and adaptive immunity 41,42 …”