Selection and design of high-affinity RNA ligands for HIV-1 Rev. NLM AIDSLINE Important note: Information in this article was accurate in 1994. The state of the art may have changed since the publication date.

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Selection and design of high-affinity RNA ligands for HIV-1 Rev.

Gene. 1993 Dec 27;137(1):19-24. Unique Identifier : AIDSLINE MED/94109690
Giver L; Bartel DP; Zapp ML; Green MR; Ellington AD; Department of Chemistry, Indiana University, Bloomington 47405.

Abstract: We have used in vitro selection to isolate minimal, high-affinity RNA ligands for the Rev protein of HIV-1. Sequence analysis reveals that the tightest binding aptamers exhibit some similarity to a Rev-binding element (RBE) localized within the Rev-responsive element (RRE), but also contain novel sequence and structural motifs. A short helical stem and bulged nucleotides (nt) CUC ... UYGAG that have no counterpart in the wild-type (wt) element contribute to high-affinity binding. We have designed and synthesized a short (37 nt) RNA molecule that incorporates this motif; this RNA ligand has from three- to fivefold tighter binding than the full-length wt element, and up to 16-fold tighter than minimal wt RBEs. A guanosine:guanosine pairing that is postulated to occur in the wt element has been altered to other base pairings in the context of our optimized minimal element. RNAs that contain non-Watson-Crick base pairings, that can be modeled as isosteric to the wt G:G pair, bind Rev up to 160-fold tighter than elements that contain canonical Watson-Crick pairings or non-isosteric mismatches. These results support the hypothesis that Rev recognizes structural features associated with a non-Watson-Crick base pair.
Keywords: Base Composition Base Sequence Gene Products, rev/*CHEMISTRY Ligands Models, Chemical Molecular Sequence Data Nucleic Acid Conformation Protein Binding RNA/*CHEMICAL SYNTHESIS JOURNAL ARTICLEKWDbasecompositionbasesequencegeneproducts,rev/KWDchemistryligandsmodels,chemicalmolecularsequencedatanucleicacidconformationproteinbindingrna/KWDchemicalsynthesisjournalarticle
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M9440027

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