Nucleolar Sequestration of Rta of Epstein-Barr VI Rus by Mcrs2

Rta is a transcription factor expressed during the immediate-early stage of the Epstein-Barr virus (EBV) lytic cycle. This protein activates the transcription of EBV lytic genes and is critical to EBV lytic development. This study finds that Rta is a binding partner of a nucleolar protein, MCRS2, in yeast. The interaction is verified in vitro by GST-pulldown and in vivo by coimmunoprecipitation. A confocal microscopy work also reveals the colocalization of these two proteins in the nucleolus, implying that MCRS2 causes the sequestration of Rta in the nucleolus. In transient transfection assay, this study shows that MCRS2 represses the activations of the BRLF1 promoter (Rp) and a promoter that contains an Rta response element (RRE), suggesting that sequestration of Rta in the nucleolus inhibits Rta’s capacity to activate RNA polymerase II-driven transcription. Additionally, this study provides compelling evidences, which show that Rta is expressed and sequestered in the nucleolus during EBV latency in Akata and P3HR1 cells. During EBV latency, Rta appears to enhance the transcription of rDNA gene. To elucidate the significance of Rta expression, this study will investigate (a) how the sequestration of Rta in the nucleolus affects the EBV lytic cycle, (b) how sequestration of Rta influences the EBV latent cycle, (c) how Rta influences the transcription of the rDNA gene, and (d) how Rta gene is transcribed during viral latency. This study will reveal important functions of Rta, which will lead to a better understanding on how the expression of Rta influences EBV and its host cells.

Project ID:PC10108-0435
External Project ID:NSC101-2320-B182-014-MY3