Type I arginine methyltransferases are intervention points to unveil the oncogenic Epstein-Barr virus to the immune system
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00209805%3A_____%2F22%3A00079100" target="_blank" >RIV/00209805:_____/22:00079100 - isvavai.cz</a>
Result on the web
<a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9723642/pdf/gkac915.pdf" target="_blank" >https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9723642/pdf/gkac915.pdf</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1093/nar/gkac915" target="_blank" >10.1093/nar/gkac915</a>
Alternative languages
Result language
angličtina
Original language name
Type I arginine methyltransferases are intervention points to unveil the oncogenic Epstein-Barr virus to the immune system
Original language description
The oncogenic Epstein-Barr virus (EBV) evades the immune system but has an Achilles heel: its genome maintenance protein EBNA1. Indeed, EBNA1 is essential for viral genome maintenance but is also highly antigenic. Hence, EBV seemingly evolved a system in which the glycine-alanine repeat (GAr) of EBNA1 limits the translation of its own mRNA to the minimal level to ensure its essential function, thereby, at the same time, minimizing immune recognition. Therefore, defining intervention points at which to interfere with GAr-based inhibition of translation is an important step to trigger an immune response against EBV-carrying cancers. The host protein nucleolin (NCL) plays a critical role in this process via a direct interaction with G-quadruplexes (G4) formed in the GAr-encoding sequence of the viral EBNA1 mRNA. Here we show that the C-terminal arginine-glycine-rich (RGG) motif of NCL is crucial for its role in GAr-based inhibition of translation by mediating interaction of NCL with G4 of EBNA1 mRNA. We also show that this interaction depends on the type I arginine methyltransferase family, notably PRMT1 and PRMT3: drugs or small interfering RNA that target these enzymes prevent efficient binding of NCL on G4 of EBNA1 mRNA and relieve GAr-based inhibition of translation and of antigen presentation. Hence, this work defines type I arginine methyltransferases as therapeutic targets to interfere with EBNA1 and EBV immune evasion.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10608 - Biochemistry and molecular biology
Result continuities
Project
<a href="/en/project/EF16_019%2F0000868" target="_blank" >EF16_019/0000868: Molecular, cellular and clinical approach to healthy ageing</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2022
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
NUCLEIC ACIDS RESEARCH
ISSN
0305-1048
e-ISSN
1362-4962
Volume of the periodical
50
Issue of the periodical within the volume
20
Country of publishing house
GB - UNITED KINGDOM
Number of pages
21
Pages from-to
11799-11819
UT code for WoS article
000880346800001
EID of the result in the Scopus database
2-s2.0-85143551812