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Journal of Virology, November 2001, p. 10359-10371, Vol. 75, No. 21
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.21.10359-10371.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

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

Christine Magin-Lachmann,dagger Silvia Hahn, Heike Strobel, Ulrike Held, Johannes Löwer,* and Roswitha Löwer

Paul-Ehrlich-Institut, D-63225 Langen, Germany

Received 10 January 2001/Accepted 18 July 2001

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.

* Corresponding author. Mailing address: Paul-Ehrlich-Institut, Paul-Ehrlich Str. 51-59, D-63225 Langen, Germany. Phone: 49-6103-77340. Fax: 49-6103-771252. E-mail: loero{at}pei.de.

dagger Present address: Boehringer Ingelheim Austria, Vienna, Austria.

Journal of Virology, November 2001, p. 10359-10371, Vol. 75, No. 21
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.21.10359-10371.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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