RNA stability of the E2A-encoded transcription factor E47 is lower in splenic activated B cel ls from aged mice

Daniela Frasca, Elaine Van der Put, Ana Marie Landin, Dapeng Gong, Richard L Riley, Bonnie B Blomberg

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Abstract

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 mMNA stability in both young and old B cells, further stressing the role of p38 MAPK in E2A MNA 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.

Original languageEnglish
Pages (from-to)6633-6644
Number of pages12
JournalJournal of Immunology
Volume175
Issue number10
StatePublished - Nov 15 2005

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RNA Stability
B-Lymphocytes
Transcription Factors
p38 Mitogen-Activated Protein Kinases
Messenger RNA
DNA-Binding Proteins
Proteolysis
Signal Transduction

ASJC Scopus subject areas

  • Immunology

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RNA stability of the E2A-encoded transcription factor E47 is lower in splenic activated B cel ls from aged mice. / Frasca, Daniela; Van der Put, Elaine; Landin, Ana Marie; Gong, Dapeng; Riley, Richard L; Blomberg, Bonnie B.

In: Journal of Immunology, Vol. 175, No. 10, 15.11.2005, p. 6633-6644.

Research output: Contribution to journalArticle

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