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Review
. 2021 Sep 24:12:731842.
doi: 10.3389/fimmu.2021.731842. eCollection 2021.

N6 -Methyladenosine and Rheumatoid Arthritis: A Comprehensive Review

Sha Wu  1 , Xiao-Feng Li  1   2 , Yuan-Yuan Wu  1 , Su-Qin Yin  1 , Cheng Huang  1 , Jun Li  1
Affiliations
Review

N6 -Methyladenosine and Rheumatoid Arthritis: A Comprehensive Review

Sha Wu et al. Front Immunol. .

Abstract

Rheumatoid arthritis (RA), one of the most common autoimmune diseases, is characterized by immune cell infiltration, fibroblast-like synovial cell hyperproliferation, and cartilage and bone destruction. To date, numerous studies have demonstrated that immune cells are one of the key targets for the treatment of RA. N6-methyladenosine (m6A) is the most common internal modification to eukaryotic mRNA, which is involved in the splicing, stability, export, and degradation of RNA metabolism. m6A methylated-related genes are divided into writers, erasers, and readers, and they are critical for the regulation of cell life. They play a significant role in various biological processes, such as virus replication and cell differentiation by controlling gene expression. Furthermore, a growing number of studies have indicated that m6A is associated with the occurrence of numerous diseases, such as lung cancer, bladder cancer, gastric cancer, acute myeloid leukemia, and hepatocellular carcinoma. In this review, we summarize the history of m6A research and recent progress on RA research concerning m6A enzymes. The relationship between m6A enzymes, immune cells, and RA suggests that m6A modification offers evidence for the pathogenesis of RA, which will help in the development of new therapies for RA.

Keywords: N6-methyladenosine; autoimmune disease; cancers; immune cells; rheumatoid arthritis.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Time for discovery and functions of m6A-related enzymes and proteins.
Figure 2
Figure 2
Research progress on METTL3, which is one of the most studied genes in m6A methylation.
Figure 3
Figure 3
mRNA expression of m6A-related enzymes was quantified using qRT-PCR in the synovial tissues of RA and osteoarthritis patients. The histogram represents multiple expressions of m6A-related enzymes in RA. The expression in osteoarthritis is 1. Values represent means ± standard deviations. ## p < 0.01 vs. OA; # p < 0.05 vs. OA.
Figure 4
Figure 4
The complexes formed by METTL3, METTL14, WTAP, and RBM15 are common writers; those formed by ALKBH5 and FTO are common erasers; and those formed by YTHDC1, YTHDF1, and YTHDF3 are common readers. M6A methylation is involved in a wide range of biological regulatory processes in the innate and adaptive immune systems, such as adjustment of signaling pathways, differentiation, translation of immune transcripts. It controls the production of inflammatory factors, inflammation-related signaling pathways, and other genes that have a direct impact on RA. It is worth noting that, m6A methylation may also directly affect synovial cell proliferation and tumor tissue, which may be a potential discovery in future RA research.
See this image and copyright information in PMC

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