Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Gene. 1993 Dec 27;137(1):19-24.

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

Author information

  • 1Department 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.

PMID:
7506689
[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Write to the Help Desk