Using viral species specificity to define a critical protein/RNA interaction surface

The Tap protein mediates the sequence-specific nuclear export of mRNAs bear ing the retroviral constitutive transport element (CTE) and also plays a cr itical role in the sequence nonspecific export of cellular mRNAs. Previousl y, we have demonstrated that CTE function displays species specificity, tha t is, the CTE functions in human but not quail cells. Here, we demonstrate that quail Tap fails to support CTE function because it cannot bind the CTE . However, changing a single residue in quail Tap, glutamine 246, to argini ne, the residue found in human Tap, rescues both CTE function and CTE bindi ng. This residue, which is located on the exterior of a recently reported m olecular structure of Tap, defines a surface on Tap that is critical for CT E binding. These data emphasize the potential importance of cross-species g enetic complementation in the identification and characterization of cellul ar factors that are critical for different aspects of viral replication.