The miR-155-PU.1 axis acts on Pax5 to enable efficient terminal B cell differentiation
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
WEHI Research Division(s)
Molecular Immunology
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
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