EBNA-1, the major nuclear antigen of Epstein-Barr virus, resembles 'RGG' RNA binding proteins

Nuclear antigen 1 (EBNA-1) is one of the key functions of the oncogenic DNA virus, Epstein-Barr virus (EBV), and is the only viral protein consistently expressed in EBV-associated malignancies. EBNA-1 binds in a site-specific manner to the viral DNA and is essential for viral replication, as well as for maintaining the genome as an extrachromosomal episome within infected cells. EBNA-1 is not recognized by the cellular immune system. Here we demonstrate that, in addition to its known DNA binding properties, EBNA-1 can also act as a strong RNA binding protein, interacting with diverse substrates in vitro, including the EBV-encoded RNA polymerase III transcript EBER1 and the HIV-encoded transactivation response (TAR) element. We also show that EBNA-1 can bind exon sequences derived from its own RNA expressed from the Fp promoter, as found in Burkitt's lymphoma-related cells and in nasopharyngeal carcinomas. EBNA-1 has been identified as a component in an RNA complex; moreover, an anti-EBNA-1 antibody 1H4-1, that does not inhibit DNA binding, blocks binding to RNA. Arginine/glycine-containing (so-called 'RGG') motifs have been found in an increasing number of proteins that interact with RNA. The EBV antigen contains three potential 'RGG' motifs located around an internal glycine/alanine-rich repetitive sequence in the protein, and outside the region of EBNA-1 mapped previously as essential for viral DNA replication and other functionally defined properties. These motifs could be involved in the observed binding between EBNA-1 and RNA.(ABSTRACT TRUNCATED AT 250 WORDS)