A Single miRNA-mRNA Interaction Affects the Immune Response in a Context- and Cell-Type-Specific Manner

Immunity. 2015 Jul 21;43(1):52-64. doi: 10.1016/j.immuni.2015.04.022. Epub 2015 Jul 7.


MicroRNA (miRNA)-dependent regulation of gene expression confers robustness to cellular phenotypes and controls responses to extracellular stimuli. Although a single miRNA can regulate expression of hundreds of target genes, it is unclear whether any of its distinct biological functions can be due to the regulation of a single target. To explore in vivo the function of a single miRNA-mRNA interaction, we mutated the 3' UTR of a major miR-155 target (SOCS1) to specifically disrupt its regulation by miR-155. We found that under physiologic conditions and during autoimmune inflammation or viral infection, some immunological functions of miR-155 were fully or largely attributable to the regulation of SOCS1, whereas others could be accounted only partially or not at all by this interaction. Our data suggest that the role of a single miRNA-mRNA interaction is dependent on cell type and biological context.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / genetics
  • Animals
  • CD8-Positive T-Lymphocytes / immunology*
  • Encephalomyelitis, Autoimmune, Experimental / genetics
  • Encephalomyelitis, Autoimmune, Experimental / immunology
  • Gene Expression Profiling
  • Herpesviridae Infections / immunology
  • Herpesviridae Infections / virology
  • Killer Cells, Natural / immunology*
  • Killer Cells, Natural / transplantation
  • Lymphocytic Choriomeningitis / immunology
  • Lymphocytic Choriomeningitis / virology
  • Lymphocytic choriomeningitis virus / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • MicroRNAs / genetics*
  • Muromegalovirus / immunology
  • Mutation
  • RNA, Messenger / genetics
  • Suppressor of Cytokine Signaling 1 Protein
  • Suppressor of Cytokine Signaling Proteins / genetics*
  • T-Lymphocytes, Regulatory / immunology*


  • 3' Untranslated Regions
  • MicroRNAs
  • Mirn155 microRNA, mouse
  • RNA, Messenger
  • Socs1 protein, mouse
  • Suppressor of Cytokine Signaling 1 Protein
  • Suppressor of Cytokine Signaling Proteins

Associated data

  • GEO/GSE68511