title: A Single miRNA-mRNA Interaction Affects the Immune Response in a Context- and Cell-Type-Specific Manner.
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.
authors.affiliation: 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.
authors.forename: Li-Fan
authors.initials: LF
authors.lastname: Lu
authors.affiliation: 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.
authors.forename: Georg
authors.initials: G
authors.lastname: Gasteiger
authors.affiliation: Laboratory Animal Center, College of Medicine, National Taiwan University, Taipei 100, Taiwan.
authors.forename: I-Shing
authors.initials: IS
authors.lastname: Yu
authors.affiliation: Howard Hughes Medical Institute and Immunology Program, and Ludwig Center, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Ashutosh
authors.initials: A
authors.lastname: Chaudhry
authors.affiliation: Howard Hughes Medical Institute and Immunology Program, and Ludwig Center, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Jing-Ping
authors.initials: JP
authors.lastname: Hsin
authors.affiliation: Computational Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Yuheng
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Howard Hughes Medical Institute and Immunology Program, and Ludwig Center, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Paula D
authors.initials: PD
authors.lastname: Bos
authors.affiliation: 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.
authors.forename: Ling-Li
authors.initials: LL
authors.lastname: Lin
authors.affiliation: Howard Hughes Medical Institute and Immunology Program, and Ludwig Center, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Carolyn L
authors.initials: CL
authors.lastname: Zawislak
authors.affiliation: Division of Biological Sciences and Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Sunglim
authors.initials: S
authors.lastname: Cho
authors.affiliation: Howard Hughes Medical Institute and Immunology Program, and Ludwig Center, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Sun
authors.affiliation: Computational Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Christina S
authors.initials: CS
authors.lastname: Leslie
authors.affiliation: 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.
authors.forename: Shu-Wha
authors.initials: SW
authors.lastname: Lin
authors.affiliation: 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.
authors.forename: Alexander Y
authors.initials: AY
authors.lastname: Rudensky
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology; D020869:Gene Expression Profiling; D006566:Herpesviridae Infections / Q000276:immunology / Q000821:virology; D007694:Killer Cells, Natural / Q000276:immunology* / Q000637:transplantation; D008216:Lymphocytic Choriomeningitis / Q000276:immunology / Q000821:virology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics*; D018146:Muromegalovirus / Q000276:immunology; D009154:Mutation; D012333:RNA, Messenger / Q000235:genetics; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D020413:3' Untranslated Regions; D035683:MicroRNAs; C532623:Mirn155 microRNA, mouse; D012333:RNA, Messenger; C491590:Socs1 protein, mouse; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins