The miR-155-PU.1 axis acts on Pax5 to enable efficient terminal B cell differentiation

LU, D., NAKAGAWA, R., LAZZARO, S., STAUDACHER, P., ABREU-GOODGER, C., HENLEY, T., BOIANI, S, LEYLAND, Rebecca, GALLOWAY, A., ANDREWS, S., BUTCHER, G., NUTT, S.L., TURNER, M. and VIGORITO, E. (2014). The miR-155-PU.1 axis acts on Pax5 to enable efficient terminal B cell differentiation. Journal of Experimental Medicine, 211 (11), 2183-2198.

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Open Access URL: https://rupress.org/jem/article/211/11/2183/41469/... (Published version)
Link to published version:: https://doi.org/10.1084/jem.20140338
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    Abstract

    © 2014 Lu et al. 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.

    Item Type: Article
    Uncontrolled Keywords: 3' Untranslated Regions; Animals; Antibody Formation; B-Lymphocytes; Base Sequence; Binding Sites; Cell Adhesion; Cell Communication; Cell Differentiation; Gene Expression Regulation; Lymphocyte Activation; Lymphopoiesis; Mice; Mice, Knockout; MicroRNAs; Myelopoiesis; PAX5 Transcription Factor; Positive Regulatory Domain I-Binding Factor 1; Proto-Oncogene Proteins; T-Lymphocytes; Trans-Activators; Transcription Factors; B-Lymphocytes; T-Lymphocytes; Animals; Mice, Knockout; Mice; Trans-Activators; Proto-Oncogene Proteins; Transcription Factors; MicroRNAs; 3' Untranslated Regions; Lymphocyte Activation; Cell Adhesion; Cell Communication; Cell Differentiation; Lymphopoiesis; Myelopoiesis; Antibody Formation; Gene Expression Regulation; Binding Sites; Base Sequence; PAX5 Transcription Factor; Positive Regulatory Domain I-Binding Factor 1; 11 Medical and Health Sciences; Immunology
    Identification Number: https://doi.org/10.1084/jem.20140338
    Page Range: 2183-2198
    SWORD Depositor: Symplectic Elements
    Depositing User: Symplectic Elements
    Date Deposited: 18 Feb 2021 11:24
    Last Modified: 17 Mar 2021 15:00
    URI: http://shura.shu.ac.uk/id/eprint/28173

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