The miR-155–PU. 1 axis acts on Pax5 to enable efficient terminal B cell differentiation
D Lu, R Nakagawa, S Lazzaro, P Staudacher… - Journal of Experimental …, 2014 - rupress.org
D Lu, R Nakagawa, S Lazzaro, P Staudacher, C Abreu-Goodger, T Henley, S Boiani…
Journal of Experimental Medicine, 2014•rupress.orgA 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 …
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 …
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.
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