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Journal of Virology, February 2009, p. 1289-1298, Vol. 83, No. 3
0022-538X/09/$08.00+0     doi:10.1128/JVI.01369-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

mRNA Translation Regulation by the Gly-Ala Repeat of Epstein-Barr Virus Nuclear Antigen 1{triangledown}

Sebastien Apcher,1,{dagger} Anastassia Komarova,1,{dagger},{ddagger} Chrysoula Daskalogianni,1 Yili Yin,2 Laurence Malbert-Colas,1 and Robin Fåhraeus1*

INSERM Unité 716, Institut de Génétique Moléculaire, Université Paris 7, Hôpital St. Louis, 27 rue Juliette Dodu, 75010 Paris, France,1 College of Life Sciences, University of Dundee, MSI/WTB/JBC Complex, Dundee DD1 5EH, United Kingdom2

Received 1 July 2008/ Accepted 10 November 2008

The glycine-alanine repeat (GAr) sequence of the Epstein-Barr virus-encoded EBNA-1 prevents presentation of antigenic peptides to major histocompatibility complex class I molecules. This has been attributed to its capacity to suppress mRNA translation in cis. However, the underlying mechanism of this function remains largely unknown. Here, we have further investigated the effect of the GAr as a regulator of mRNA translation. Introduction of silent mutations in each codon of a 30-amino-acid GAr sequence does not significantly affect the translation-inhibitory capacity, whereas minimal alterations in the amino acid composition have strong effects, which underscores the observation that the amino acid sequence and not the mRNA sequence mediates GAr-dependent translation suppression. The capacity of the GAr to repress translation is dose and position dependent and leads to a relative accumulation of preinitiation complexes on the mRNA. Taken together with the surprising observation that fusion of the 5' untranslated region (UTR) of the c-myc mRNA to the 5' UTR of GAr-carrying mRNAs specifically inactivates the effect of the GAr, these results indicate that the GAr targets components of the translation initiation process. We propose a model in which the nascent GAr peptide delays the assembly of the initiation complex on its own mRNA.

* Corresponding author. Mailing address: INSERM Unité 716, Institut de Génétique Moléculaire, Université Paris 7, Hôpital St. Louis, 27 rue Juliette Dodu, 75010 Paris, France. Phone: 33 142 499269. Fax: 33 142494838. E-mail: robin.fahraeus{at}inserm.fr

{triangledown} Published ahead of print on 19 November 2008.

{dagger} S.A. and A.K. contributed equally to this work.

{ddagger} Present address: Laboratoire Génomique Virale et Vaccination, Institut Pasteur, 25-28 Rue du Dr. Roux, 75015 Paris, France.

Journal of Virology, February 2009, p. 1289-1298, Vol. 83, No. 3
0022-538X/09/$08.00+0     doi:10.1128/JVI.01369-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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