Journal article
The miR-155-PU.1 axis acts on Pax5 to enable efficient terminal B cell differentiation
D Lu, R Nakagawa, S Lazzaro, P Staudacher, C Abreu-Goodger, T Henley, S Boiani, R Leyland, A Galloway, S Andrews, G Butcher, SL Nutt, M Turner, E Vigorito
Journal of Experimental Medicine | ROCKEFELLER UNIV PRESS | Published : 2014
DOI: 10.1084/jem.20140338
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 g..
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Awarded by UK Research and Innovation
Funding Acknowledgements
This work was supported by the Medical Research Council through a CDA fellowship (G0700287) and grant (G1001781) to EV as well as funding from the BBSRC. SLN is supported by an Australian Research Council Future Fellowship. This work was made possible through Victorian State Government Operational Infrastructure Support and Australian Government NHMRC IRIIS.