Protein Rex

UniProtKB accession:  P0C206

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UniProtKB description:  Rex escorts unspliced gag-pro-pol and singly spliced env mRNAs out of the nucleus of infected cells. These mRNAs carry a recognition sequence called Rex responsive element (RxRE or XRE) located at the 3' region of the long terminal repeat (LTR). This function is essential since most HTLV proteins are translated from unspliced or partially spliced pre-mRNAs that cannot exit the nucleus by the pathway used by fully processed cellular mRNAs. Rex itself is translated from a fully spliced mRNA that probably readily exits the nucleus. Rex's nuclear localization signal (NLS) binds directly to KPNB1/importin beta-1 without previous binding to KPNA1/importin alpha-1. KPNB1 binds to the GDP bound form of RAN (Ran-GDP) and targets Rex to the nucleus. In the nucleus, the conversion from Ran-GDP to Ran-GTP dissociates Rex from KPNB1 and allows Rex's binding to the RRE in viral pre-mRNAs. Rex multimerizes on the RRE via cooperative assembly. This multimerization is critical for its full biological activity, since it may shield the viral RNA from being spliced or down-regulated, and probably exposes Rex's nuclear export signal (NES) to the surface. Rex can then form a complex with XPO1/CRM1, RANBP3 and Ran-GTP, leading to nuclear export of the complex. Conversion from Ran-GTP to Ran-GDP mediates dissociation of the Rex/RRE/XPO1/RANBP3/RAN complex, so that Rex can return to the nucleus for a subsequent round of export (By similarity).