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The miR-155-PU.1 axis acts on Pax5 to enable efficient terminal B cell differentiation.
Lu, Dong; Nakagawa, Rinako; Lazzaro, Sandra; Staudacher, Philipp; Abreu-Goodger, Cei; Henley, Tom; Boiani, Sara; Leyland, Rebecca; Galloway, Alison; Andrews, Simon; Butcher, Geoffrey; Nutt, Stephen L; Turner, Martin; Vigorito, Elena.
Affiliation
  • Lu D; Lymphocyte Signaling and Development and The Bioinformatics Group, The Babraham Institute, Babraham Research Campus, Cambridge, Cambridgeshire CB22 3AT, England, UK.
  • Nakagawa R; Lymphocyte Signaling and Development and The Bioinformatics Group, The Babraham Institute, Babraham Research Campus, Cambridge, Cambridgeshire CB22 3AT, England, UK.
  • Lazzaro S; Lymphocyte Signaling and Development and The Bioinformatics Group, The Babraham Institute, Babraham Research Campus, Cambridge, Cambridgeshire CB22 3AT, England, UK.
  • Staudacher P; Lymphocyte Signaling and Development and The Bioinformatics Group, The Babraham Institute, Babraham Research Campus, Cambridge, Cambridgeshire CB22 3AT, England, UK.
  • Abreu-Goodger C; National Laboratory of Genomics for Biodiversity (Langbio), Cinvestav, Irapuato, 36821 Guanajuato, Mexico.
  • Henley T; Lymphocyte Signaling and Development and The Bioinformatics Group, The Babraham Institute, Babraham Research Campus, Cambridge, Cambridgeshire CB22 3AT, England, UK.
  • Boiani S; Lymphocyte Signaling and Development and The Bioinformatics Group, The Babraham Institute, Babraham Research Campus, Cambridge, Cambridgeshire CB22 3AT, England, UK.
  • Leyland R; Lymphocyte Signaling and Development and The Bioinformatics Group, The Babraham Institute, Babraham Research Campus, Cambridge, Cambridgeshire CB22 3AT, England, UK.
  • Galloway A; Lymphocyte Signaling and Development and The Bioinformatics Group, The Babraham Institute, Babraham Research Campus, Cambridge, Cambridgeshire CB22 3AT, England, UK.
  • Andrews S; Lymphocyte Signaling and Development and The Bioinformatics Group, The Babraham Institute, Babraham Research Campus, Cambridge, Cambridgeshire CB22 3AT, England, UK.
  • Butcher G; Lymphocyte Signaling and Development and The Bioinformatics Group, The Babraham Institute, Babraham Research Campus, Cambridge, Cambridgeshire CB22 3AT, England, UK.
  • Nutt SL; The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia 3010, Australia Department of Medical Biology, University of Melbourne, Parkville, Victoria 3010, Australia.
  • Turner M; 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.
  • Vigorito E; 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.
J Exp Med ; 211(11): 2183-98, 2014 Oct 20.
Article in En | MEDLINE | ID: mdl-25288398
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.
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Full text: 1 Database: MEDLINE Main subject: B-Lymphocytes / Cell Differentiation / Trans-Activators / Proto-Oncogene Proteins / MicroRNAs / PAX5 Transcription Factor Limits: Animals Language: En Journal: J Exp Med Year: 2014 Type: Article Affiliation country: United kingdom
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Full text: 1 Database: MEDLINE Main subject: B-Lymphocytes / Cell Differentiation / Trans-Activators / Proto-Oncogene Proteins / MicroRNAs / PAX5 Transcription Factor Limits: Animals Language: En Journal: J Exp Med Year: 2014 Type: Article Affiliation country: United kingdom