Details

Autor(en) / Beteiligte

• Iizasa, Hisashi
• Wulff, Bjorn-Erik
• Alla, Nageswara R.
• Maragkakis, Manolis
• Megraw, Molly
• Hatzigeorgiou, Artemis
• Iwakiri, Dai
• Takada, Kenzo
• Wiedmer, Andreas
• Showe, Louise
• Lieberman, Paul
• Nishikura, Kazuko

Titel

Editing of Epstein-Barr Virus-encoded BART6 MicroRNAs Controls Their Dicer Targeting and Consequently Affects Viral Latency

Ist Teil von

• The Journal of biological chemistry, 2010-10, Vol.285 (43), p.33358-33370

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2010

Quelle

MEDLINE

Beschreibungen/Notizen

• Certain primary transcripts of miRNA (pri-microRNAs) undergo RNA editing that converts adenosine to inosine. The Epstein-Barr virus (EBV) genome encodes multiple microRNA genes of its own. Here we report that primary transcripts of ebv-miR-BART6 (pri-miR-BART6) are edited in latently EBV-infected cells. Editing of wild-type pri-miR-BART6 RNAs dramatically reduced loading of miR-BART6-5p RNAs onto the microRNA-induced silencing complex. Editing of a mutation-containing pri-miR-BART6 found in Daudi Burkitt lymphoma and nasopharyngeal carcinoma C666-1 cell lines suppressed processing of miR-BART6 RNAs. Most importantly, miR-BART6-5p RNAs silence Dicer through multiple target sites located in the 3′-UTR of Dicer mRNA. The significance of miR-BART6 was further investigated in cells in various stages of latency. We found that miR-BART6-5p RNAs suppress the EBNA2 viral oncogene required for transition from immunologically less responsive type I and type II latency to the more immunoreactive type III latency as well as Zta and Rta viral proteins essential for lytic replication, revealing the regulatory function of miR-BART6 in EBV infection and latency. Mutation and A-to-I editing appear to be adaptive mechanisms that antagonize miR-BART6 activities.