Document Detail


The miR-155-PU.1 axis acts on Pax5 to enable efficient terminal B cell differentiation.
MedLine Citation:
PMID:  25288398     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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.
Authors:
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
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-10-6
Journal Detail:
Title:  The Journal of experimental medicine     Volume:  -     ISSN:  1540-9538     ISO Abbreviation:  J. Exp. Med.     Publication Date:  2014 Oct 
Date Detail:
Created Date:  2014-10-7     Completed Date:  -     Revised Date:  2014-10-8    
Medline Journal Info:
Nlm Unique ID:  2985109R     Medline TA:  J Exp Med     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2014 Lu et al.
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