A peptide encoded by pri‐miRNA‐31 represses autoimmunity by promoting Treg differentiation. (28th March 2022)

• Record Type: Journal Article
• Authors: Zhou, Hong; Lou, Fangzhou; Bai, Jing; Sun, Yang; Cai, Wei; Sun, Libo; Xu, Zhenyao; Liu, Zhaoyuan; Zhang, Lingyun; Yin, Qianqian; Zhang, Junxun; Gao, Yuanyuan; Wang, Zhikai; Niu, Liman; Cai, Xiaojie; Deng, Siyu; Wang, Hong; Xia, Li; Ginhoux, Florent; Li, Qun; Wang, Honglin
• Is Part Of: EMBO reports. Volume 23:Number 5(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-03-28
• Subjects: autoimmune disease -- miPEP31 -- miR‐31 -- transcriptional repressor -- Treg; Molecular biology -- Periodicals; Molecular Biology -- Periodicals; Molecular biology; Periodicals; 572.8
• DOI: 10.15252/embr.202153475
• Languages: English
• ISSNs: 1469-221X

Abstract

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. Synopsis: miPEP31, encoded by the primary transcript of miR‐31, is a cell‐penetrating peptide which promotes Treg differentiation. Synthesized miPEP31 enhances the induction of peripheral Tregs and suppresses experimental autoimmune encephalomyelitis. miPEP31 is a peptide of 44 amino acids encoded by pri‐miR‐31. miPEP31 promotes Treg differentiation. miPEP31 suppresses experimental autoimmune encephalomyelitis (EAE). miPEP31 directly inhibits miR‐31 transcription. Abstract : miPEP31, encoded by the primary transcript of miR‐31, is a cell‐penetrating peptide which promotes Treg differentiation. Synthesized miPEP31 enhances the induction of peripheral Tregs and suppresses experimental autoimmune encephalomyelitis.