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

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 disr...

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Detalles Bibliográficos
Autores principales: Lu, Dong, Nakagawa, Rinako, Lazzaro, Sandra, Staudacher, Philipp, Abreu-Goodger, Cei, Henley, Tom, Boiani, Sara, Leyland, Rebecca, Galloway, Alison, Andrews, Simon, Butcher, Geoffrey, Nutt, Stephen L., Turner, Martin, Vigorito, Elena
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4203942/
https://www.ncbi.nlm.nih.gov/pubmed/25288398
http://dx.doi.org/10.1084/jem.20140338
Descripción
Sumario: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.