%0 Journal Article %J J Biol Chem %D 2010 %T Editing of Epstein-Barr virus-encoded BART6 microRNAs controls their dicer targeting and consequently affects viral latency. %A Iizasa, Hisashi %A Wulff, Bjorn-Erik %A Alla, Nageswara R %A Maragkakis, Manolis %A Megraw, Molly %A Hatzigeorgiou, Artemis %A Iwakiri, Dai %A Takada, Kenzo %A Wiedmer, Andreas %A Showe, Louise %A Lieberman, Paul %A Nishikura, Kazuko %K Cell Line, Tumor %K Epstein-Barr Virus Infections %K Epstein-Barr Virus Nuclear Antigens %K Gene Silencing %K Herpesvirus 4, Human %K Humans %K Immediate-Early Proteins %K MicroRNAs %K Ribonuclease III %K RNA Editing %K RNA, Viral %K Trans-Activators %K Viral Proteins %K Virus Latency %X

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.

%B J Biol Chem %V 285 %P 33358-70 %8 2010 Oct 22 %G eng %N 43 %R 10.1074/jbc.M110.138362