|Title||Editing of Epstein-Barr virus-encoded BART6 microRNAs controls their dicer targeting and consequently affects viral latency.|
|Publication Type||Journal Article|
|Year of Publication||2010|
|Authors||Iizasa, H, Wulff, B-E, Alla, NR, Maragkakis, M, Megraw, M, Hatzigeorgiou, A, Iwakiri, D, Takada, K, Wiedmer, A, Showe, L, Lieberman, P, Nishikura, K|
|Journal||J Biol Chem|
|Date Published||2010 Oct 22|
|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|
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.
|Alternate Journal||J. Biol. Chem.|
|PubMed Central ID||PMC2963350|
|Grant List||CA010815 / CA / NCI NIH HHS / United States |
GM040536 / GM / NIGMS NIH HHS / United States
HL099342 / HL / NHLBI NIH HHS / United States
Editing of Epstein-Barr virus-encoded BART6 microRNAs controls their dicer targeting and consequently affects viral latency.
Submitted by Megraw Lab Admin on Tue, 2016-07-12 22:11