title: The miR-155-PU.1 axis acts on Pax5 to enable efficient terminal B cell differentiation.
abstract: A single microRNA (miRNA) can regulate the expression of many genes, though the level of repression imparted on any given target is generally low. How then is the selective pressure for a single miRNA/target interaction maintained across long evolutionary distances? We addressed this problem by disrupting in vivo the interaction between miR-155 and PU.1 in mice. Remarkably, this interaction proved to be key to promoting optimal T cell-dependent B cell responses, a previously unrecognized role for PU.1. Mechanistically, miR-155 inhibits PU.1 expression, leading to Pax5 down-regulation and the initiation of the plasma cell differentiation pathway. Additional PU.1 targets include a network of genes whose products are involved in adhesion, with direct links to B-T cell interactions. We conclude that the evolutionary adaptive selection of the miR-155-PU.1 interaction is exercised through the effectiveness of terminal B cell differentiation.
authors.affiliation: Lymphocyte Signaling and Development and The Bioinformatics Group, The Babraham Institute, Babraham Research Campus, Cambridge, Cambridgeshire CB22 3AT, England, UK.
authors.forename: Dong
authors.initials: D
authors.lastname: Lu
authors.affiliation: Lymphocyte Signaling and Development and The Bioinformatics Group, The Babraham Institute, Babraham Research Campus, Cambridge, Cambridgeshire CB22 3AT, England, UK.
authors.forename: Rinako
authors.initials: R
authors.lastname: Nakagawa
authors.affiliation: Lymphocyte Signaling and Development and The Bioinformatics Group, The Babraham Institute, Babraham Research Campus, Cambridge, Cambridgeshire CB22 3AT, England, UK.
authors.forename: Sandra
authors.initials: S
authors.lastname: Lazzaro
authors.affiliation: Lymphocyte Signaling and Development and The Bioinformatics Group, The Babraham Institute, Babraham Research Campus, Cambridge, Cambridgeshire CB22 3AT, England, UK.
authors.forename: Philipp
authors.initials: P
authors.lastname: Staudacher
authors.affiliation: National Laboratory of Genomics for Biodiversity (Langbio), Cinvestav, Irapuato, 36821 Guanajuato, Mexico.
authors.forename: Cei
authors.initials: C
authors.lastname: Abreu-Goodger
authors.affiliation: Lymphocyte Signaling and Development and The Bioinformatics Group, The Babraham Institute, Babraham Research Campus, Cambridge, Cambridgeshire CB22 3AT, England, UK.
authors.forename: Tom
authors.initials: T
authors.lastname: Henley
authors.affiliation: Lymphocyte Signaling and Development and The Bioinformatics Group, The Babraham Institute, Babraham Research Campus, Cambridge, Cambridgeshire CB22 3AT, England, UK.
authors.forename: Sara
authors.initials: S
authors.lastname: Boiani
authors.affiliation: Lymphocyte Signaling and Development and The Bioinformatics Group, The Babraham Institute, Babraham Research Campus, Cambridge, Cambridgeshire CB22 3AT, England, UK.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Leyland
authors.affiliation: Lymphocyte Signaling and Development and The Bioinformatics Group, The Babraham Institute, Babraham Research Campus, Cambridge, Cambridgeshire CB22 3AT, England, UK.
authors.forename: Alison
authors.initials: A
authors.lastname: Galloway
authors.affiliation: Lymphocyte Signaling and Development and The Bioinformatics Group, The Babraham Institute, Babraham Research Campus, Cambridge, Cambridgeshire CB22 3AT, England, UK.
authors.forename: Simon
authors.initials: S
authors.lastname: Andrews
authors.affiliation: Lymphocyte Signaling and Development and The Bioinformatics Group, The Babraham Institute, Babraham Research Campus, Cambridge, Cambridgeshire CB22 3AT, England, UK.
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Butcher
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia 3010, Australia Department of Medical Biology, University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Nutt
authors.affiliation: Lymphocyte Signaling and Development and The Bioinformatics Group, The Babraham Institute, Babraham Research Campus, Cambridge, Cambridgeshire CB22 3AT, England, UK martin.turner@babraham.ac.uk elena.vigorito@babraham.ac.uk.
authors.forename: Martin
authors.initials: M
authors.lastname: Turner
authors.affiliation: Lymphocyte Signaling and Development and The Bioinformatics Group, The Babraham Institute, Babraham Research Campus, Cambridge, Cambridgeshire CB22 3AT, England, UK martin.turner@babraham.ac.uk elena.vigorito@babraham.ac.uk.
authors.forename: Elena
authors.initials: E
authors.lastname: Vigorito
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D000917:Antibody Formation / Q000235:genetics / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D001483:Base Sequence; D001665:Binding Sites; D002448:Cell Adhesion / Q000235:genetics; D002450:Cell Communication / Q000235:genetics / Q000276:immunology; D002454:Cell Differentiation / Q000235:genetics*; D005786:Gene Expression Regulation; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D038041:Lymphopoiesis / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000737:chemistry / Q000235:genetics*; D038042:Myelopoiesis / Q000235:genetics; D051757:PAX5 Transcription Factor / Q000737:chemistry / Q000235:genetics*; D000074462:Positive Regulatory Domain I-Binding Factor 1; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000235:genetics*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D015534:Trans-Activators / Q000737:chemistry / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics; D000099232:Proto-Oncogene Protein Spi-1
chemical_list: D020413:3' Untranslated Regions; D035683:MicroRNAs; D051757:PAX5 Transcription Factor; D000074462:Positive Regulatory Domain I-Binding Factor 1; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D000099232:Proto-Oncogene Protein Spi-1; C532623:Mirn155 microRNA, mouse; C497282:Pax5 protein, mouse; C513258:Prdm1 protein, mouse