The molecular structure and biological functions of RNA methylation, with special emphasis on the roles of RNA methylation in autoimmune diseases

Abstract

Autoimmune diseases such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and systemic vasculitis are caused by the body's immune response to autoantigens. The pathogenesis of autoimmune diseases is complex. RNA methylation is known to play a key role in disease progression as it regulates almost all aspects of RNA processing, including RNA nuclear export, translation, splicing, and noncoding RNA processing. This review summarizes the mechanisms, molecular structures of RNA methylations and their roles in biological functions. Similar to the roles of RNA methylation in cancers, RNA methylation in RA and SLE involves “writers” that deposit methyl groups to form N6-methyladenosine (m6A) and 5-methylcytosine (m5C), “erasers” that remove these modifications, and “readers” that further affect mRNA splicing, export, translation, and degradation. Recent advances in detection methods have identified N1-methyladenosine (m1A), N6,2-O-dimethyladenosine (m6Am), and 7-methylguanosine (m7G) RNA modifications, and their roles in RA and SLE need to be further studied. The relationship between RNA methylation and other autoimmune diseases has not been reported, and the roles and mechanisms of RNA modifications in these diseases need to be explored in the future.

Keywords:

• RNA methylation
• autoimmune diseases
• m6A
• m5C
• rheumatoid arthritis
• systemic lupus erythematosus

Acknowledgments

Wanwan Zhou is a graduate student in the School of Integrated Chinese and Western Medicine of the Anhui University of Chinese Medicine. She assisted Professor Miao in collecting published articles, writing this review, and undertaking research in this field.

Xiao Wang is a lecturer in the School of Nursing of the Anhui University of Chinese Medicine and a member of our research group. Xiao Wang assisted Professor Miao in revising the manuscript, supplementing the contents of the manuscript, and undertaking research in this field.

Jun Chang is the director of the Department of Orthopaedics, the Fourth Affiliated Hospital of Anhui Medical University, and is a Doctor of Medicine. He was responsible for assisting Professor Miao in writing the molecular structure of RNA methylations and participated in the revision of the manuscript.

Chenglong Cheng is a graduate student in the School of Integrated Chinese and Western Medicine of the Anhui University of Chinese Medicine. He assisted Professor Miao in writing this review and undertaking research in this field.

Chenggui Miao is a professor in the Department of Pharmacology, School of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, and a professor in the Institute of Prevention and Treatment of Rheumatoid Arthritis, the First Affiliated Hospital of the Anhui University of Chinese Medicine. He was responsible for the design and writing of this review, including the molecular structures and biological functions of RNA methylation and its roles in autoimmune diseases.

Disclosure statement

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

Additional information

Funding

This project was supported by the National Science Foundation of China (No. 81302783), the Anhui Province Key Research and Development Plan (No.1804a0802218), the Excellent Talent Project of Anhui Science and Technology University (No. XJYXRC201801), and the special support plan of high-level talent introduction of Anhui University of Chinese Medicine (No.2020rcZD001).