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Journal Article | Research Support, Non-U.S. Gov't | Research Support, U.S. Gov't, Non-P.H.S. | Research Support, U.S. Gov't, P.H.S.

High-resolution mapping of the human T-cell leukemia virus type 1 Rex-binding element by in vitro selection.

S Baskerville, M Zapp, A D Ellington
S Baskerville
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M Zapp
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A D Ellington
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ABSTRACT

Interactions between the Rex protein of HTLV-1 and the genomic Rex-binding element (XBE) mediate the cytoplasmic transport of viral mRNAs. However, it is uncertain which RNA sequences and structures contribute to Rex recognition. A portion of the viral genome that spanned the XBE was partially randomized, and functional Rex-binding variants were selected. Alignment of selected Rex-binding sequences revealed positions that were functionally conserved between different molecules. A model is presented in which a subset of the selected residues are in direct contact with Rex. Positions that covaried with one another were also found. These covariations support a secondary-structural model in which a central paired stem is symmetrically flanked by two bulge loops. On the basis of this model, site-directed mutations of the XBE were constructed and each half molecule was found to bind independently to Rex. The functional residues and secondary structures in the XBE half molecules bear a remarkable resemblance to the transactivation response region element of HIV-1. Since the transactivation response region element is known to interact specifically with arginine residues in the Tat protein, these results suggest that the XBE binds to the arginine-rich RNA-binding domain of Rex in a similar manner. This model is supported by the selection data.

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High-resolution mapping of the human T-cell leukemia virus type 1 Rex-binding element by in vitro selection.
S Baskerville, M Zapp, A D Ellington
Journal of Virology Dec 1995, 69 (12) 7559-7569; DOI:

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High-resolution mapping of the human T-cell leukemia virus type 1 Rex-binding element by in vitro selection.
S Baskerville, M Zapp, A D Ellington
Journal of Virology Dec 1995, 69 (12) 7559-7569; DOI:
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