Editing of Epstein-Barr virus-encoded BART6 microRNAs controls their dicer targeting and consequently affects viral

Hisashi Iizasa1, Bjorn-Erik Wulff2, Nageswara R Alla2

  • 1From the The Wistar Institute, Philadelphia, Pennsylvania 19104; Institute for Genetic Medicine, Hokkaido University, Sapporo 060-0815, Japan.

Insights

Epstein-Barr virus (EBV) microRNAs are edited, affecting their function and viral latency. RNA editing and mutations antagonize EBV microRNA activity, impacting viral oncogene and replication protein suppression.

Area of Science:

  • Molecular Biology
  • Virology
  • Epigenetics

Background:

  • Primary microRNAs (pri-microRNAs) can undergo RNA editing, specifically adenosine to inosine conversion.
  • The Epstein-Barr virus (EBV) genome encodes its own microRNA genes.

Purpose of the Study:

  • To investigate RNA editing of EBV-encoded pri-miR-BART6 in latently infected cells.
  • To determine the functional consequences of pri-miR-BART6 editing on miR-BART6 activity and EBV infection.

Main Methods:

  • Analysis of pri-miR-BART6 RNA editing in EBV-infected cell lines.
  • Assessment of microRNA loading onto the microRNA-induced silencing complex.
  • Investigation of miR-BART6 target gene regulation (Dicer mRNA).
  • Evaluation of miR-BART6-5p activity in different EBV latency stages.

Main Results:

  • Pri-miR-BART6 RNAs are edited in latently EBV-infected cells.
  • Editing of wild-type pri-miR-BART6 reduced miR-BART6-5p loading onto the silencing complex.
  • Editing of mutated pri-miR-BART6 suppressed miR-BART6 processing.
  • miR-BART6-5p silences Dicer mRNA and suppresses EBNA2, Zta, and Rta viral proteins.
  • miR-BART6-5p activity is regulated during different EBV latency stages.

Conclusions:

  • RNA editing and mutations in pri-miR-BART6 serve as adaptive mechanisms to antagonize miR-BART6 functions.
  • miR-BART6 plays a regulatory role in EBV infection, latency, and replication.
  • Understanding these mechanisms provides insights into EBV pathogenesis and viral control.

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