02615nas a2200445 4500008004100000022001400041245012900055210006900184260001600253300001300269490000800282520127800290653002101568653003401589653004001623653001901663653002501682653001101707653002901718653001401747653002101761653001601782653001501798653002101813653001901834653001801853100002001871700002201891700002301913700002401936700001801960700002701978700001702005700001802022700002102040700001802061700002002079700002202099856004802121 2010 eng d a1083-351X00aEditing of Epstein-Barr virus-encoded BART6 microRNAs controls their dicer targeting and consequently affects viral latency.0 aEditing of EpsteinBarr virusencoded BART6 microRNAs controls the c2010 Oct 22 a33358-700 v2853 a
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.
10aCell Line, Tumor10aEpstein-Barr Virus Infections10aEpstein-Barr Virus Nuclear Antigens10aGene Silencing10aHerpesvirus 4, Human10aHumans10aImmediate-Early Proteins10aMicroRNAs10aRibonuclease III10aRNA Editing10aRNA, Viral10aTrans-Activators10aViral Proteins10aVirus Latency1 aIizasa, Hisashi1 aWulff, Bjorn-Erik1 aAlla, Nageswara, R1 aMaragkakis, Manolis1 aMegraw, Molly1 aHatzigeorgiou, Artemis1 aIwakiri, Dai1 aTakada, Kenzo1 aWiedmer, Andreas1 aShowe, Louise1 aLieberman, Paul1 aNishikura, Kazuko uhttp://megraw.cgrb.oregonstate.edu/node/323