A peptide encoded by pri-miRNA-31 represses autoimmunity by promoting Treg differentiation.

Abstract

Recent evidence has revealed that small polypeptides (containing fewer than 100 amino acids) can be translated from noncoding RNAs (ncRNAs), which are usually defined as RNA molecules that do not encode proteins. However, studies on functional products translated from primary transcripts of microRNA (pri-miRNA) are quite limited. Here, we describe a peptide termed miPEP31 that is encoded by pri-miRNA-31. miPEP31 is highly expressed in Foxp3+ regulatory T cells (Tregs ) and significantly promotes the differentiation of Tregs without affecting their inhibitory ability. Our results show that miPEP31 is a cell-penetrating peptide both in vitro and in vivo. miPEP31 downregulates miR-31 expression, enhances peripheral Treg induction, and dramatically suppresses experimental autoimmune encephalomyelitis. Mechanistically, we show that miPEP31 acts as a transcriptional repressor inhibiting the expression of miRNA-31, a negative regulator of Tregs . Our results reveal an indispensable role of miPEP31 in maintaining immune homeostasis by promoting Treg differentiation and also present a potential therapeutic peptide for modulating miRNA expression and treating autoimmune diseases.

• Authors: Hong Zhou, Fangzhou Lou, Jing Bai, Yang Sun, Wei Cai, Libo Sun, Zhenyao Xu, Zhaoyuan Liu, Lingyun Zhang, Qianqian Yin, Junxun Zhang, Yuanyuan Gao, Zhikai Wang, Liman Niu, Xiaojie Cai, Siyu Deng, Hong Wang, Li Xia, Florent Ginhoux, Qun Li, Honglin Wang
• Journal: EMBO reports (EMBO Rep) Vol. 23 Issue 5 Pg. e53475 (05 04 2022) ISSN: 1469-3178 [Electronic] England
• PMID: 35343645 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2022 The Authors.

Chemical References

• MicroRNAs
• Peptides

Topics

• Animals
• Autoimmunity (genetics)
• Encephalomyelitis, Autoimmune, Experimental
• MicroRNAs (genetics, metabolism)
• Peptides (genetics, metabolism, pharmacology)
• T-Lymphocytes, Regulatory (metabolism)