Rev

After transcription from the integrated DNA genome, the unspliced and partially-spliced viral mRNAs, encoding structural proteins and genomic RNA to be packaged into virions, are exported from the nucleus to the cytoplasm by the regulatory protein Rev. This activity involves the binding of approximately 6-10 Rev subunits to the Rev Response Element (RRE) located in an intronic region of the unspliced transcripts. Rev then interacts with the host protein Crm1 (Exportin 1), forming a complex with GTP-bound Ran. This entire RNA-protein complex is then moved through the nuclear pore and released in the cytoplasm.

The HARC Center Rev project, headed by Dr. Alan Frankel, builds upon previous work by Dr. Frankel and other members of the HARC Center, including detailed biochemical and biophysical analyses of Rev-RRE binding as well as a collaboration that produced the NMR structure of the Rev arginine-rich motif (ARM)-RRE RNA complex. Specifically, the Rev project is aimed at determining structures of Rev in complex with its various binding partners, using NMR, crystallography and cryo-EM, with the goal of understanding the Rev-RRE oligomeric complex and its interactions with the CRM1 export receptor.