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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, R; Galloway, A; Andrews, S; Butcher, G; Nutt, SL; Turner, M; Vigorito, E
2014-10-06
J Exp Med
Journal Article
211
11
2183-98
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.
Rockefeller University Press
Molecular Immunology
10.1084/jem.20140338
This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org.ezp.lib.unimelb.edu.au/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).

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Creation Date 2014-10-13 02:21:51 Last Modified 2015-05-26 09:36:09