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The expression of a viral microRNA is regulated by clustering to allow optimal B cell transformation.
Nucleic Acids Res. 44, 1326-1341 (2016)
The Epstein-Barr virus (EBV) transforms B cells by expressing latent proteins and the BHRF1 microRNA cluster. MiR-BHRF1-3, its most transforming member, belongs to the recently identified group of weakly expressed microRNAs. We show here that miR-BHRF1-3 displays an unusually low propensity to form a stem-loop structure, an effect potentiated by miR-BHRF1-3's proximity to the BHRF1 polyA site. Cloning miR-BHRF1-2 or a cellular microRNA, but not a ribozyme, 5' of miR-BHRF1-3 markedly enhanced its expression. However, a virus carrying mutated miR-BHRF1-2 seed regions expressed miR-BHRF1-3 at normal levels and was fully transforming. Therefore, miR-BHRF1-2's role during transformation is independent of its seed regions, revealing a new microRNA function. Increasing the distance between miR-BHRF1-2 and miR-BHRF1-3 in EBV enhanced miR-BHRF1-3's expression but decreased its transforming potential. Thus, the expression of some microRNAs must be restricted to a narrow range, as achieved by placing miR-BHRF1-3 under the control of miR-BHRF1-2.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Rna Secondary Structure; Selective 2'-hydroxyl Acylation; Single Nucleotide Resolution; Virus-encoded Micrornas; Primer Extension Shape; In-vivo; Structure Prediction; Tertiary Structure; Mirna Biogenesis; Cancer
ISSN (print) / ISBN
0305-1048
e-ISSN
1362-4962
Journal
Nucleic Acids Research
Quellenangaben
Volume: 44,
Issue: 3,
Pages: 1326-1341
Publisher
Oxford University Press
Publishing Place
Oxford
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Institute of Diabetes and Obesity (IDO)