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Ayoubian, H.* ; Fröhlich, T.* ; Pogodski, D.* ; Flatley, A. ; Kremmer, E. ; Schepers, A. ; Feederle, R. ; Arnold, G.J.* ; Grässer, F.A.*

Antibodies against the mono-methylated arginine-glycine repeat (MMA-RG) of the Epstein-Barr virus nuclear antigen 2 (EBNA2) identify potential cellular proteins targeted in viral transformation.

J. Gen. Virol. 98, 2128-2142 (2017)
Verlagsversion Forschungsdaten DOI PMC
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
The Epstein-Barr virus is a human herpes virus with oncogenic potential. The virus-encoded nuclear antigen 2 (EBNA2) is a key mediator of viral tumorigenesis. EBNA2 features an arginine-glycine (RG) repeat at amino acids (aa)339-354 that is essential for the transformation of lymphocytes and contains symmetrically (SDMA) and asymmetrically (ADMA) di-methylated arginine residues. The SDMA-modified EBNA2 binds the survival motor neuron protein (SMN), thus mimicking SMD3, a cellular SDMA-containing protein that interacts with SMN. Accordingly, a monoclonal antibody (mAb) specific for the SDMA-modified RG repeat of EBNA2 also binds to SMD3. With the novel mAb 19D4 we now show that EBNA2 contains mono-methylated arginine (MMA) residues within the RG repeat. Using 19D4, we immune-precipitated and analysed by mass spectrometry cellular proteins in EBV-transformed B-cells that feature MMA motifs that are similar to the one in EBNA2. Among the cellular proteins identified, we confirmed by immunoprecipitation and/or Western blot analyses Aly/REF, Coilin, DDX5, FXR1, HNRNPK, LSM4, MRE11, NRIP, nucleolin, PRPF8, RBM26, SMD1 (SNRDP1) and THRAP3 proteins that are either known to contain MMA residues or feature RG repeat sequences that probably serve as methylation substrates. The identified proteins are involved in splicing, tumorigenesis, transcriptional activation, DNA stability and RNA processing or export. Furthermore, we found that several proteins involved in energy metabolism are associated with MMA-modified proteins. Interestingly, the viral EBNA1 protein that features methylated RG repeat motifs also reacted with the antibodies. Our results indicate that the region between aa 34-52 of EBNA1 contains ADMA or SDMA residues, while the region between aa 328-377 mainly contains MMA residues.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Arginine-methylation ; Epstein-barr Virus ; Ebna1 ; Ebna2 Monoclonal Antibodies ; Mass Spectrometry Analysis ; Mono-methyl-arginine; Spinal Muscular-atrophy; Motor-neuron Protein; Messenger-rna; Sm Proteins; Proteomic Analysis; 20s Complex; Cells; Transcription; Recruitment; Interacts
ISSN (print) / ISBN 0022-1317
e-ISSN 1465-2099
Zeitschrift Journal of General Virology
Quellenangaben Band: 98, Heft: 8, Seiten: 2128-2142 Artikelnummer: , Supplement: ,
Verlag Society for General Microbiology
Verlagsort London
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) CF Monoclonal Antibodies (CF-MAB)
Research Unit Gene Vector (AGV)