General effect of Sam68 on Rev/Rex regulated expression of complex retroviruses

Abstract

We have previously demonstrated that overexpression of Sam68 functionally substitutes for, as well as synergizes with, HIV-1 Rev in RRE-mediated gene expression and virus replication. In addition, C-terminal deletion mutants of Sam68 exhibit a transdominant negative phenotype in HIV replication. We now report that Sam68 also enhances the activities of Rev-like proteins of other complex retroviruses (e.g. HTLV-1 and EIAV) on their respective RNA targets. Furthermore, we demonstrate that Sam68 can function alone as well as synergize with Rev-MS2 and/or Rex-MS2 chimeric proteins on expression mediated by the corresponding RRE-MS2 fusion RNA element. Additionally, dominant negative mutants of Sam68 also repressed the synergistic activation of Sam68 with Rex, E-Rev, and/or Rev-MS2/Rex-MS2 on their corresponding RNA targets. Thus, Sam68 may play an important role in the post-transcriptional regulation of all complex retroviruses.