The miR-155-PU.1 axis acts on Pax5 to enable efficient terminal B cell differentiation.
J Exp Med
; 211(11): 2183-98, 2014 Oct 20.
Article
in En
| MEDLINE
| ID: mdl-25288398
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.
Full text:
1
Database:
MEDLINE
Main subject:
B-Lymphocytes
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Cell Differentiation
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Trans-Activators
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Proto-Oncogene Proteins
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MicroRNAs
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PAX5 Transcription Factor
Limits:
Animals
Language:
En
Journal:
J Exp Med
Year:
2014
Type:
Article
Affiliation country:
United kingdom