Intron retention may regulate expression of Epstein-Barr virus nuclear antigen 3 family genes

Kienzle, Norbert, Young, David B., Liaskou, Daphne, Buck, Marion, Greco, Sonia and Sculley, Tom B. (1999) Intron retention may regulate expression of Epstein-Barr virus nuclear antigen 3 family genes. Journal of Virology, 73 2: 1195-1204.

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Author Kienzle, Norbert
Young, David B.
Liaskou, Daphne
Buck, Marion
Greco, Sonia
Sculley, Tom B.
Title Intron retention may regulate expression of Epstein-Barr virus nuclear antigen 3 family genes
Journal name Journal of Virology   Check publisher's open access policy
ISSN 0022-538X
Publication date 1999-01-01
Sub-type Article (original research)
Open Access Status File (Publisher version)
Volume 73
Issue 2
Start page 1195
End page 1204
Total pages 10
Place of publication Baltimore, U.S.A.
Publisher Williams & Wilkins
Language eng
Subject C1
321020 Pathology
730102 Immune system and allergy
Abstract The nuclear antigen 3 family genes (EBNA-3, EBNA-4, and EBNA-6) of Epstein-Barr virus (EBV) are important for EBV-induced immortalization and survival of B lymphocytes. However, little is known about how the expression of these genes is regulated. Each of the EBNA-3, EBNA-4 and EBNA-6 genes consists of two exons separated by a small intron. Reverse transcriptase PCR assays revealed that the vast majority of the EBNA-3, EBNA-4, and EBNA-6 mRNA, expressed in transfected and EBV-infected B cells, retained intron sequences. Northern blot and S1 protection assays confirmed that most of the EBNA-3 mRNA contained intron. Examination of deletion mutants of EBNA-3 indicated that the EBNA-3 protein was not necessary for intron retention and that there was no splicing silencing element encoded in the EBNA-3 mRNA. Cell fractionation and RNA gradient analysis revealed that the unspliced EBNA 3 family mRNAs were transported into the cytoplasm and associated with the polysomes. However, Western blot analysis of FLAG-epitope tagged EBNA-3 gave no indication of the presence of splice variant protein forms of EBNA-3. In contrast, transiently transfected cells expressing EBNA-3 revealed a sixfold increase in EBNA-3 protein expression from the genomic EBNA-3 gene compared to EBNA-3 cDNA. These data show that the intronic sequences can influence EBNA-3 protein expression and suggest that intron retention may provide a means for the fine-tuning of expression of the individual EBNA 3 family genes.
Keyword Virology
Latent Membrane-protein
Splice-site Selection
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
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Citation counts: TR Web of Science Citation Count  Cited 17 times in Thomson Reuters Web of Science Article | Citations
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Created: Wed, 11 Jun 2008, 00:11:10 EST