The Epstein-Barr virus miR-BHRF1 microRNAs regulate viral gene expression in cis.
The Epstein-Barr virus (EBV) miR-BHRF1 microRNA (miRNA) cluster has been shown to facilitate B-cell transformation and promote the rapid growth of the resultant lymphoblastoid cell lines (LCLs). However, we find that expression of physiological levels of the miR-BHRF1 miRNAs in LCLs transformed with a miR-BHRF1 null mutant (∆123) fails to increase their growth rate. We demonstrate that the pri-miR-BHRF1-2 and 1-3 stem-loops are present in the 3'UTR of transcripts encoding EBNA-LP and that excision of pre-miR-BHRF1-2 and 1-3 by Drosha destabilizes these mRNAs and reduces expression of the encoded protein. Therefore, mutational inactivation of pri-miR-BHRF1-2 and 1-3 in the ∆123 mutant upregulates the expression of not only EBNA-LP but also EBNA-LP-regulated mRNAs and proteins, including LMP1. We hypothesize that this overexpression causes the reduced transformation capacity of the ∆123 EBV mutant. Thus, in addition to regulating cellular mRNAs in trans, miR-BHRF1-2 and 1-3 also regulate EBNA-LP mRNA expression in cis.
Duke Scholars
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- Virology
- RNA, Viral
- MicroRNAs
- Humans
- Herpesvirus 4, Human
- Gene Expression Regulation, Viral
- Cell Line
- 32 Biomedical and clinical sciences
- 31 Biological sciences
- 30 Agricultural, veterinary and food sciences
Citation
Published In
DOI
EISSN
Publication Date
Volume
Start / End Page
Location
Related Subject Headings
- Virology
- RNA, Viral
- MicroRNAs
- Humans
- Herpesvirus 4, Human
- Gene Expression Regulation, Viral
- Cell Line
- 32 Biomedical and clinical sciences
- 31 Biological sciences
- 30 Agricultural, veterinary and food sciences