BLIMP-1 and STAT3 counterregulate microRNA-21 during plasma cell differentiation.
J Immunol
; 189(1): 253-60, 2012 Jul 01.
Article
in En
| MEDLINE
| ID: mdl-22634616
ABSTRACT
During cellular differentiation, mRNA transcription and translation require precise coordination. The mechanisms controlling this are not well defined. IL-21 is an important regulator of plasma cell differentiation, and it controls the master regulator of plasma cell differentiation, B lymphocyte-induced maturation protein-1 (BLIMP-1), via STAT3 and IRF4. Among the other targets of STAT3 is microRNA-21 (miR-21). miR-21 is the most frequently deregulated microRNA in malignancy, including B cell lymphomas, and it has oncogenic potential downstream of STAT3. However, the regulation and function of miR-21 during plasma cell differentiation are not characterized. In contrast to the induction of miR-21 observed in response to STAT3 activation in other systems, we demonstrate that miR-21 is repressed during IL-21-driven plasma cell differentiation. We explored the molecular basis for this repression and identify primary miR-21 transcription as a direct target of BLIMP-1-dependent repression, despite continued STAT3 activation and phospho-STAT3 binding to the primary miR-21 promoter. Thus, STAT3 and BLIMP-1 constitute an incoherent feed-forward loop downstream of IL-21 that can coordinate microRNA with mRNA expression during plasma cell differentiation.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Plasma Cells
/
Repressor Proteins
/
Cell Differentiation
/
Feedback, Physiological
/
MicroRNAs
/
STAT3 Transcription Factor
Type of study:
Prognostic_studies
Limits:
Animals
/
Humans
Language:
En
Journal:
J Immunol
Year:
2012
Document type:
Article
Affiliation country:
United kingdom