The Epstein–Barr virus noncoding RNA EBER2 transactivates the UCHL1 deubiquitinase to accelerate cell growth

Zhe Li, Francesco Baccianti, Susanne Delecluse, Ming Han Tsai, Anatoliy Shumilov, Xianliang Cheng, Sicong Ma, Ingrid Hoffmann, Remy Poirey, Henri Jacques Delecluse*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

The Epstein–Barr virus (EBV) transforms resting B cells and is involved in the development of B cell lymphomas. We report here that the viral noncoding RNA EBER2 accelerates B cell growth by potentiating expression of the UCHL1 deubiquitinase that itself increased expression of the Aurora kinases and of cyclin B1. Importantly, this effect was also visible in Burkitt’s lymphoma cells that express none of the virus’s known oncogenes. Mechanistically, EBER2 bound the UCHL1 messenger RNA (mRNA), thereby bringing a protein complex that includes PU.1, a UCHL1 transactivator, to the vicinity of its promoter. Although the EBV oncogene LMP1 has been suggested to induce UCHL1, we show here that EBER2 plays a much more important role to reach significant levels of the deubiquitinase in infected cells. However, some viruses that carried a polymorphic LMP1 had an increased ability to achieve full UCHL1 expression. This work identifies a direct cellular target of a viral noncoding RNA that is likely to be central to EBV’s oncogenic properties.

Original languageEnglish
Article numbere2115508118
JournalProceedings of the National Academy of Sciences of the United States of America
Volume118
Issue number43
DOIs
StatePublished - 26 Oct 2021

Keywords

  • B cell lymphomas
  • Epstein–Barr virus
  • Noncoding RNA EBER2
  • UCHL1

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