Journal Article

DKFZ-2021-02326

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png The Epstein-Barr virus noncoding RNA EBER2 transactivates the UCHL1 deubiquitinase to accelerate cell growth.

Li, Z. (First author)DKFZ* ; Baccianti, F.DKFZ* ; Delecluse, S.DKFZ* ; Tsai, M.-H. ; Shumilov, A.DKFZ* ; Cheng, X.DKFZ* ; Ma, S.DKFZ* ; Hoffmann, I.DKFZ* ; Poirey, R.DKFZ* ; Delecluse, H.-J. (Last author)DKFZ*

2021
National Acad. of Sciences Washington, DC

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Please use a persistent id in citations: doi:10.1073/pnas.2115508118

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.

Keyword(s): B cell lymphomas ; Epstein–Barr virus ; UCHL1 ; noncoding RNA EBER2

Note: #EA:F100#LA:F100#

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Contributing Institute(s):

1. F100 Pathologie infektionsbedingter Tumoren (F100)
2. T-Zell-Metabolismus (D192)
3. F045 Zellzykluskontrolle und Karzinogenese (F045)

Research Program(s):

1. 316 - Infektionen, Entzündung und Krebs (POF4-316) (POF4-316)

Appears in the scientific report 2021

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; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Agriculture, Biology and Environmental Sciences ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 5 ; JCR ; National-Konsortium ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection ; Zoological Record

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