The Epstein-Barr virus noncoding RNA EBER2 transactivates the UCHL1 deubiquitinase to accelerate cell growth.
Proc Natl Acad Sci U S A
; 118(43)2021 10 26.
Article
in En
| MEDLINE
| ID: mdl-34686609
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
RNA, Viral
/
Transcriptional Activation
/
Herpesvirus 4, Human
/
Cell Proliferation
/
Deubiquitinating Enzymes
Limits:
Humans
Language:
En
Journal:
Proc Natl Acad Sci U S A
Year:
2021
Type:
Article
Affiliation country:
Germany