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 encodes the regulatory protein Rec (formerly designated Corf), which is functionally equivalent to the nuclear export adapter proteins Rev of human immunodeficiency virus and Rex of human T-cell leukemia virus. We have demonstrated that the Rec protein interacts with a characteristic 429-nucleotide RNA element, the Rec-responsive element (RcRE), present in the 3' long terminal repeat of HTDV/HERV-K transcripts. In analogy to the Rev and Rex proteins, 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 abrogate Rec function. In addition, we demonstrate that Rec function requires binding to a complex, folded RNA structure rather than binding to a discrete specific binding site, in contrast to Rev and Rex and their homologous responsive elements. We define four stem-loop structures in the RcRE that are essential for Rec function. Finally, we demonstrate that both Rev and Rex can mediate nuclear export through the RcRE but that their binding sites are different from each other and from that of Rec.
Magin-Lachmann
C
C
Paul-Ehrlich-Institut, D-63225 Langen, Germany.
Hahn
S
S
Strobel
H
H
Held
U
U
Löwer
J
J
Löwer
R
R
D001483:Base Sequence; D001665:Binding Sites; D002467:Cell Nucleus / Q000378:metabolism; D020077:Endogenous Retroviruses / Q000235:genetics*; D015694:Gene Products, rev / Q000502:physiology; D016370:Gene Products, rex / Q000502:physiology; D008969:Molecular Sequence Data; D012313:RNA / Q000737:chemistry* / Q000378:metabolism; D020218:Response Elements; D012191:Retroviridae Proteins / Q000502:physiology*; D020079:Terminal Repeat Sequences
D015694:Gene Products, rev; D016370:Gene Products, rex; D012191:Retroviridae Proteins; D012313:RNA