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

Dong Lu, Rinako Nakagawa, Sandra Lazzaro, Philipp Staudacher, Cei Abreu-Goodger, Tom Henley, Sara Boiani, Rebecca Leyland, Alison Galloway, Simon Andrews, Geoffrey Butcher, Stephen L. Nutt, Martin Turner, Elena Vigorito

Research output: Contribution to journalArticlepeer-review

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.
Original languageEnglish
Pages (from-to)2183–2198
Number of pages19
JournalJournal of Experimental Medicine
Volume211
Issue number11
DOIs
Publication statusPublished - 6 Oct 2014

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