@article {323, title = {Editing of Epstein-Barr virus-encoded BART6 microRNAs controls their dicer targeting and consequently affects viral latency.}, journal = {J Biol Chem}, volume = {285}, year = {2010}, month = {2010 Oct 22}, pages = {33358-70}, abstract = {

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\&$\#$39;-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.

}, keywords = {Cell Line, Tumor, Epstein-Barr Virus Infections, Epstein-Barr Virus Nuclear Antigens, Gene Silencing, Herpesvirus 4, Human, Humans, Immediate-Early Proteins, MicroRNAs, Ribonuclease III, RNA Editing, RNA, Viral, Trans-Activators, Viral Proteins, Virus Latency}, issn = {1083-351X}, doi = {10.1074/jbc.M110.138362}, author = {Iizasa, Hisashi and Wulff, Bjorn-Erik and Alla, Nageswara R and Maragkakis, Manolis and Megraw, Molly and Hatzigeorgiou, Artemis and Iwakiri, Dai and Takada, Kenzo and Wiedmer, Andreas and Showe, Louise and Lieberman, Paul and Nishikura, Kazuko} }