A micropeptide encoded by lncRNA MIR155HG suppresses autoimmune inflammation via modulating antigen presentation.

Science Advances
Liman NiuHonglin Wang

Abstract

Many annotated long noncoding RNAs (lncRNAs) harbor predicted short open reading frames (sORFs), but the coding capacities of these sORFs and the functions of the resulting micropeptides remain elusive. Here, we report that human lncRNA MIR155HG encodes a 17-amino acid micropeptide, which we termed miPEP155 (P155). MIR155HG is highly expressed by inflamed antigen-presenting cells, leading to the discovery that P155 interacts with the adenosine 5'-triphosphate binding domain of heat shock cognate protein 70 (HSC70), a chaperone required for antigen trafficking and presentation in dendritic cells (DCs). P155 modulates major histocompatibility complex class II-mediated antigen presentation and T cell priming by disrupting the HSC70-HSP90 machinery. Exogenously injected P155 improves two classical mouse models of DC-driven auto inflammation. Collectively, we demonstrate the endogenous existence of a micropeptide encoded by a transcript annotated as "non-protein coding" and characterize a micropeptide as a regulator of antigen presentation and a suppressor of inflammatory diseases.

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Citations

Nov 17, 2020·Wiley Interdisciplinary Reviews. RNA·Sara J Johnson, Thomas A Cooper
Oct 13, 2020·The Journal of Pathology·Sibrandes Poppema
Jan 29, 2021·Cellular and Molecular Life Sciences : CMLS·Rui VitorinoNobuyoshi Akimitsu
Dec 3, 2020·OncoTargets and Therapy·Ling ShenXiaoyuan Xu
Nov 27, 2020·Frontiers in Immunology·John V ForresterMirela Delibegovic
Feb 2, 2021·Frontiers in Oncology·Jiani XingLihong Wang
Feb 18, 2021·The FEBS Journal·Dörte Schlesinger, Simon J Elsässer

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Datasets Mentioned

BETA
GM-CSF

Methods Mentioned

BETA
immunoprecipitation
PCR
Fluorescence imaging
electrophoresis
pull-down
RNA-seq
proximity ligation assay
confocal microscopy
Fluorescence
flow cytometry

Software Mentioned

GraphPad Prism
Cell Ranger
FlowJo
DESeq
ImageJ
PEAKS
Seurat
Adobe Photoshop
ORFfinder

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