RNA stability of the E2A-encoded transcription factor E47 is lower in splenic activated B cells from aged mice.
We have demonstrated previously that DNA binding and protein expression of the E2A-encoded transcription factor E47 are lower in nuclear extracts of activated splenic B cells from old mice. In the present study, we address how E47 protein expression is regulated in aging. Results herein show that E2A mRNA levels were decreased in stimulated splenic B cells from old as compared with young mice. RNA stability assays showed that the rate of E2A mRNA decay was accelerated in stimulated splenic B cells from old mice, but E47 protein degradation rates were comparable in young vs aged B cells, indicating that the regulation of E47 expression in activated splenic B cells occurs primarily by mRNA stability. The rates of decay of other mRNAs showed that the increased mRNA degradation in aged splenic activated B cells is not a general phenomenon but restricted to a subset of mRNAs. We next investigated the signal transduction pathways controlling E2A mRNA expression and stability and found that p38 MAPK regulates E2A mRNA expression through increased mRNA stability and is down-regulated in aged activated B cells. Results show that inhibition of p38 MAPK significantly reduces E2A mRNA stability in both young and old B cells, further stressing the role of p38 MAPK in E2A RNA stabilization. These studies demonstrate that the transcription factor E2A, critical for many aspects of B cell function, is regulated by a novel mechanism in aging.
Frasca
Daniela
D
Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, FL 33101, USA.
Van der Put
Elaine
E
Landin
Ana Marie
AM
Gong
Dapeng
D
Riley
Richard L
RL
Blomberg
Bonnie B
BB
D000375:Aging / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D001483:Base Sequence; D004247:DNA / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation; D066298:In Vitro Techniques; D047908:Intracellular Signaling Peptides and Proteins / Q000494:pharmacology; D008213:Lymphocyte Activation; D020935:MAP Kinase Signaling System; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D020871:RNA Stability; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D051820:TCF Transcription Factors / Q000235:genetics* / Q000378:metabolism; D058125:Transcription Factor 7-Like 1 Protein; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
D047908:Intracellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D051820:TCF Transcription Factors; C544913:Tcf7l1 protein, mouse; D058125:Transcription Factor 7-Like 1 Protein; C015482:protein kinase modulator; D004247:DNA; D048051:p38 Mitogen-Activated Protein Kinases