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A‐to‐I editing of EBV‐encoded microRNAs controls viral latency
Author(s) -
Nishikura Kazuko,
Iizasa Hisashi,
Wulff BjornErik,
Alla Nageswara R.
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.203.2
Subject(s) - biology , microrna , dicer , gene silencing , lytic cycle , virus latency , rna editing , virology , rna , gene , viral replication , microbiology and biotechnology , virus , genetics , rna interference
Certain primary transcripts of miRNA (pri‐miRNAs) 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 miRNA‐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.