Rec (formerly corf) function requires interaction with a complex, folded RNA structure within its responsive element rather than binding to a discrete specific binding site

It was recently reported that the human endogenous retrovirus HTDV/HERV-K e ncodes the regulatory protein Rec (formerly designated Corf), which is func tionally equivalent to the nuclear export adapter proteins Rev of human imm unodeficiency virus and Rex of human T-cell leukemia virus. We have demonst rated that the Rec protein interacts with a characteristic 429-nucleotide R NA element, the Rec-responsive element (RcRE), present in the 3' long termi nal repeat of HTDV/HERV-K transcripts. In analogy to the Rev and Rex protei ns, which have distinct RNA binding sites in their responsive elements, we have proposed that Rec may also have a defined binding site in the RcRE. In this report, we demonstrate that not every HTDV/HERV-K copy present in the human genome contains an active RcRE, and we characterize mutations that a brogate Rec function. In addition, we demonstrate that Rec function require s binding to a complex, folded RNA structure rather than binding to a discr ete specific binding site, in contrast to Rev and Rex and their homologous responsive elements. We define four stem-loop structures in the RcRE that a re essential for Rec function. Finally, we demonstrate that both Rev and Re x can mediate nuclear export through the RcRE but that their binding sites are different from each other and from that of Rec.