RNA methylation: A potential therapeutic target in autoimmune disease

Abstract

Autoimmune diseases such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and inflammatory bowel disease (IBD) are caused by the body’s immune response to autoantigens. The pathogenesis of autoimmune diseases is unclear. Numerous studies have demonstrated that RNA methylation plays a key role in disease progression, which is essential for post-transcriptional regulation and has gradually become a broad regulatory mechanism that controls gene expression in various physiological processes, including RNA nuclear output, translation, splicing, and noncoding RNA processing. Here, we outline the writers, erasers, and readers of RNA methylation, including N6-methyladenosine (m⁶A), 2'-O-methylation (Nm), 2′-O-dimethyladenosine (m⁶Am), N1-methyladenosine (m¹A), 5-methylcytidine (m⁵C) and N7-methylguanosine (m⁷G). As the role of RNA methylation modifications in the immune system and diseases is explained, the potential treatment value of these modifications has also been demonstrated. This review reports the relationship between RNA methylation and autoimmune diseases, highlighting the need for future research into the therapeutic potential of RNA modifications.

PLAIN LANGUAGE SUMMARY

Autoimmune diseases such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and inflammatory bowel disease (IBD) are caused by the body’s immune response to autoantigens. Numerous studies have demonstrated that RNA methylation plays a key role in disease progression, which is essential for post-transcriptional regulation and has gradually become a broad regulatory mechanism that controls gene expression in various physiological processes. Here, we outline the writers, erasers, and readers of RNA methylation, including N6-methyladenosine (m⁶A), 2'-O-methylation (Nm), 2′-O-dimethyladenosine (m⁶Am), N1-methyladenosine (m¹A), 5-methylcytidine (m⁵C) and N7-methylguanosine (m⁷G). This review reports the relationship between RNA methylation and autoimmune diseases, highlighting the need for future research into the therapeutic potential of RNA modifications.

GRAPHICAL ABSTRACT

Keywords:

• m⁶A
• m⁵C
• autoimmune disease
• IBD
• RNA methylation
• SLE

Authors’ contributions

Yingping Wu, Dawei Cui and Lele Li conceived the topic. Literature review, drafted the manuscript, designed the figures and tables were performed by Yingping Wu, Lele Li and Xiaoping Xia. Tian Yang, Yuchao Sun, Xueke Liu, Wei Xu, and Mei Lu polished the manuscript. The first draft of the manuscript was written by Lele Li and Xiaoping Xia and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This study was supported by the Zhejiang Provincial Natural Science Foundation of China [No. LBY21H190001 to YP Wu].