TY - JOUR T1 - Editing of Epstein-Barr virus-encoded BART6 microRNAs controls their dicer targeting and consequently affects viral latency. JF - J Biol Chem Y1 - 2010 A1 - Iizasa, Hisashi A1 - Wulff, Bjorn-Erik A1 - Alla, Nageswara R A1 - Maragkakis, Manolis A1 - Megraw, Molly A1 - Hatzigeorgiou, Artemis A1 - Iwakiri, Dai A1 - Takada, Kenzo A1 - Wiedmer, Andreas A1 - Showe, Louise A1 - Lieberman, Paul A1 - Nishikura, Kazuko KW - Cell Line, Tumor KW - Epstein-Barr Virus Infections KW - Epstein-Barr Virus Nuclear Antigens KW - Gene Silencing KW - Herpesvirus 4, Human KW - Humans KW - Immediate-Early Proteins KW - MicroRNAs KW - Ribonuclease III KW - RNA Editing KW - RNA, Viral KW - Trans-Activators KW - Viral Proteins KW - Virus Latency AB -

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.

VL - 285 IS - 43 ER -