Solution structure of the HIV-1 frameshift inducing stem-loop RNA

Nucleic Acids Res. 2003 Aug 1;31(15):4326-31. doi: 10.1093/nar/gkg654.

Abstract

The translation of reverse transcriptase and other essential viral proteins from the HIV-1 Pol mRNA requires a programmed -1 ribosomal frameshift. This frameshift is induced by two highly conserved elements within the HIV-1 mRNA: a slippery sequence comprised of a UUUUUUA heptamer, and a downstream stem-loop structure. We have determined the structure of the HIV-1 frameshift inducing RNA stem-loop, using multidimensional heteronuclear nuclear magnetic resonance (NMR) methods. The 22 nucleotide RNA solution structure [root mean squared deviation (r.m.s.d.) = 1.2 A] was determined from 475 nuclear Overhauser effect (NOE)-derived distance restrains, 20 residual dipolar couplings and direct detection of hydrogen bonds via scalar couplings. We find that the frameshift inducing stem-loop is an A-form helix capped by a structured ACAA tetraloop. The ACAA tetraloop is stabilized by an equilateral 5' and 3' stacking pattern, a sheared A-A pair and a cross-strand hydrogen bond. Unexpectedly, the ACAA tetraloop structure is nearly identical to a known tetraloop fold, previously identified in the RNase III recognition site from Saccharomyces cerevisiae.

Publication types

  • 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.

MeSH terms

  • Adenine / chemistry
  • Base Sequence
  • Frameshifting, Ribosomal
  • HIV-1 / genetics*
  • Hydrogen Bonding
  • Models, Molecular*
  • Nuclear Magnetic Resonance, Biomolecular
  • Nucleic Acid Conformation
  • RNA, Viral / chemistry*

Substances

  • RNA, Viral
  • Adenine

Associated data

  • PDB/1PJY