Translational Regulation by Rta of Epstein-Barr Virus

Rta of Epstein-Bar virus (EBV) is a transcription factor encoded by BRLF1. Since transcription of BRLF1 is strongly activated after the virus enters the lytic cycle and Rta’s expression is required for EBV lytic development, Rta is considered to be a viral lytic protein and expressed only during the lytic cycle. Contrary to what is generally believed, this study finds that Rta is expressed during viral latency and sequestered in the nucleolus. When present in the nucleolus, Rta loses it ability to activate transcription that is driven by RNA polymerase II, explaining why Rta does not activate EBV lytic genes during EBV latency. On the other hand, although Rta is present in the nucleolus, where rDNA is transcribed, Rta does not influence the transcription of rDNA. Rather, we find that Rta promotes both cap-dependent and cap-independent translation. Our earlier studies also revealed that Rta has a sequence similar to that of yeast eIF4B and promotes Zta translation from an internal translation initiation site in the intercistronic region of the BRLF1-BZLF1 bicistronic mRNA, suggesting that Rta acts as a translation initiation factor. Therefore, this investigation will test the hypothesis that Rta is incorporated into pre-ribosomes in the nucleolus, where ribosome biogenesis occurs. As ribosomes mature, Rta becomes a part of the 40S ribosome and then promotes the binding of the ribosome to the 5’ cap of mRNA to enhance translation. Similar translational activation by Rta is also proposed for translation initiation from EV71 IRES mRNA and BRLF1-BZLF1 bicistronic mRNA. This study will elucidate an important function of Rta and reveal how EBV increases translation efficiency to relieve the burden of its host after infection.

Project ID:PC10408-1721
External Project ID:MOST104-2320-B182-034-MY2