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Haar, J.* ; Contrant, M.* ; Bernhardt, K.* ; Feederle, R. ; Diederichs, S.* ; Pfeffer, S.* ; Delecluse, H.J.*

The expression of a viral microRNA is regulated by clustering to allow optimal B cell transformation.

Nucleic Acids Res. 44, 1326-1341 (2016)
Verlagsversion DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter 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
Sprache englisch
Veröffentlichungsjahr 2016
Prepublished im Jahr 2015
HGF-Berichtsjahr 2015
ISSN (print) / ISBN 0305-1048
e-ISSN 1362-4962
Quellenangaben Band: 44, Heft: 3, Seiten: 1326-1341 Artikelnummer: , Supplement: ,
Verlag Oxford University Press
Verlagsort Oxford
Begutachtungsstatus Peer reviewed
POF Topic(s) 90000 - German Center for Diabetes Research
Forschungsfeld(er) Helmholtz Diabetes Center
PSP-Element(e) G-502291-001
PubMed ID 26635399
Scopus ID 84965078753
Erfassungsdatum 2015-12-31