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The miR-155-PU.1 axis acts on Pax5 to enable efficient terminal B cell differentiation.
- Source :
-
The Journal of experimental medicine [J Exp Med] 2014 Oct 20; Vol. 211 (11), pp. 2183-98. Date of Electronic Publication: 2014 Oct 06. - Publication Year :
- 2014
-
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.<br /> (© 2014 Lu et al.)
- Subjects :
- 3' Untranslated Regions
Animals
Antibody Formation genetics
Antibody Formation immunology
B-Lymphocytes immunology
Base Sequence
Binding Sites
Cell Adhesion genetics
Cell Communication genetics
Cell Communication immunology
Gene Expression Regulation
Lymphocyte Activation genetics
Lymphocyte Activation immunology
Lymphopoiesis genetics
Mice
Mice, Knockout
MicroRNAs chemistry
Myelopoiesis genetics
PAX5 Transcription Factor chemistry
Positive Regulatory Domain I-Binding Factor 1
Proto-Oncogene Proteins chemistry
T-Lymphocytes immunology
T-Lymphocytes metabolism
Trans-Activators chemistry
Transcription Factors genetics
B-Lymphocytes cytology
B-Lymphocytes metabolism
Cell Differentiation genetics
MicroRNAs genetics
PAX5 Transcription Factor genetics
Proto-Oncogene Proteins genetics
Trans-Activators genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1540-9538
- Volume :
- 211
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- The Journal of experimental medicine
- Publication Type :
- Academic Journal
- Accession number :
- 25288398
- Full Text :
- https://doi.org/10.1084/jem.20140338