The miR-155-PU.1 axis acts on Pax5 to enable efficient terminal B cell differentiation
- Author(s)
- 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;
- Details
- Publication Year 2014-10-06,Volume 211,Issue #11,Page 2183-98
- Journal Title
- J Exp Med
- Publication Type
- Journal Article
- 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.
- Publisher
- Rockefeller University Press
- Research Division(s)
- Molecular Immunology
- Publisher's Version
- https://doi.org/10.1084/jem.20140338
- Terms of Use/Rights Notice
- 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/).
Creation Date: 2014-10-13 02:21:51
Last Modified: 2015-05-26 09:36:09