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The Original Innovative Research from Professor Honglin Wang's Team "The New Mechanism of Non-coding RNA Regulating Autoimmunity" Selected as Annual Best Paper of the EMBO Press

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Recently, the EMBO reports journal selected research articles that have attracted widespread attention or influence, and launched the "2022 Selected Papers of Editor-in-chief". Professor Wang Honglin, the clinical research institute of the shanghai general hospital, led the team to complete the original innovative research paper entitled "A peptide encoded by pri-miRNA-31 expressions autoimmunity by promoting Treg differentiation" which was selected as annual best paper of the EMBO press. At present, the paper has been authorized by the Chinese national invention patent and is actively promoting the patent transformation.

The paper reported that the non-coding RNAs the miR-31 precursor, which were traditionally thought to have no coding ability, can encode a 44 amino acid length polypeptide, and was named as micro-peptide 31 (miPEP31). The researchers firstly confirmed that the miR-31 precursor also has the ability to encode polypeptides through ribosome fingerprint, mass spectrometry and western blot. MiPEP31 is highly expressed in Treg cells and can promote the differentiation of Treg cells. MiPEP31 has very good membrane-penetrating properties and can efficiently enter immune cells in vitro experiments. In vivo experiments, a single tail vein injection can significantly increase the level of miPEP31 in immune cells, and can maintain for more than 48 hours. MiPEP31 has excellent therapeutic effect on experimental encephalomyelitis model in mice with autoimmune disease. In mechanism, miPEP31 can enter the nucleus and inhibit the translation of miR-31 precursor by binding to the promoter region of miR-31 to influence the epigenetic of its promoter region. Reduce the expression of miPEP31 and miR-31 in the way of negative feedback, promote the differentiation of Treg cells and maintain the immune balance of the body.

The study revealed the new mechanism of non-coding RNA regulating autoimmunity and provided innovative ideas and methods for clinical treatment of autoimmune diseases. MiPEP31 has good safety, and its membrane-penetrating characteristics make it have better targeting and drug potential, providing a new strategy for clinical treatment of autoimmune diseases.

It is reported that many properties of polypeptide drugs are between chemical drugs and protein drugs, and have the advantages of high activity and safety, strong specificity, good drug preparation, etc., which are widely used in clinic and have broad prospects. Recent studies have shown that non-coding RNA, which is traditionally believed to have no coding function, also has the ability to encode polypeptides. More than 210000 non-coding RNAs have been found in the human genome, far exceeding the number of protein genes (about 20000). Endogenous non-coding RNA-coding peptides existing in vivo have natural safety and effectiveness, which is a new strategy for studying peptide drugs.

The first author of the paper is Zhou Hong, an assistant researcher of Wang Honglin's team, and Li Qun, an affiliated Ruijin Hospital, is the co-author. The research was supported by the School of Basic Medicine, School of Medicine, Shanghai Jiaotong University and the Shanghai Institute of Immunology. The research was supported by the National Natural Science Foundation's original exploration program (No.82050009), the National Key Research and Development Program of the Ministry of Science and Technology (2020YFA0112900), the National Science Fund for Distinguished Young Scholars (No.81725018), the National Natural Science Foundation's key program (No.81930088), the National Natural Science Foundation's general program (No.82070509, No. 82073428), the National Natural Science Foundation's youth program (No. 82101909, No. 82103719) Shenkang Medical Development Center's three-year action plan to promote clinical skills and clinical innovation in municipal hospitals, the clinical "five new" innovative research and development project (SHDC2020CR3061B), and the Natural Science Foundation of Shanghai Municipal Science and Technology Commission (20ZR1447400) support.

Correspondent: Hong Zhou, Clinical Research Center, Yang Hu, Publicity Department, Shanghai General Hospital

Editor: Shishi Cai, Publicity Department, Shanghai General Hospital



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