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

Li-Fan Lu; Georg Gasteiger; I-Shing Yu; Ashutosh Chaudhry; Jing-Ping Hsin; Yuheng Lu; Paula D Bos; Ling-Li Lin; Carolyn L Zawislak; Sunglim Cho; Joseph C Sun; Christina S Leslie; Shu-Wha Lin; Alexander Y Rudensky

doi:10.1016/j.immuni.2015.04.022

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.

Authors

Li-Fan Lu¹, Georg Gasteiger², I-Shing Yu³, Ashutosh Chaudhry⁴, Jing-Ping Hsin⁴, Yuheng Lu⁵, Paula D Bos⁴, Ling-Li Lin¹, Carolyn L Zawislak⁴, Sunglim Cho⁶, Joseph C Sun⁴, Christina S Leslie⁵, Shu-Wha Lin⁷, Alexander Y Rudensky⁸

Affiliations

¹ Howard Hughes Medical Institute and Immunology Program, and Ludwig Center, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA; Division of Biological Sciences and Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA.
² Howard Hughes Medical Institute and Immunology Program, and Ludwig Center, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA; Institute of Medical Microbiology and Hygiene, University of Mainz Medical Centre, Mainz 55131, Germany.
³ Laboratory Animal Center, College of Medicine, National Taiwan University, Taipei 100, Taiwan.
⁴ Howard Hughes Medical Institute and Immunology Program, and Ludwig Center, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
⁵ Computational Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
⁶ Division of Biological Sciences and Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA.
⁷ Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei 100, Taiwan; Department of Laboratory Medicine, National Taiwan University Hospital, Taipei 100, Taiwan.
⁸ Howard Hughes Medical Institute and Immunology Program, and Ludwig Center, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA. Electronic address: rudenska@mskcc.org.

Abstract

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*

Substances

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

Abstract

Publication types

MeSH terms

Substances

Associated data

Grants and funding