Structure of the RNA signal essential for translational frameshifting in HIV-1

J Mol Biol. 2005 Jun 24;349(5):1024-35. doi: 10.1016/j.jmb.2005.04.045.

Abstract

Many pathogenic viruses use a programmed -1 translational frameshifting mechanism to regulate synthesis of their structural and enzymatic proteins. Frameshifting is vital for viral replication. A slippery sequence bound at the ribosomal A and P sites as well as a downstream stimulatory RNA structure are essential for frameshifting. Conflicting data have been reported concerning the structure of the downstream RNA signal in human immunodeficiency virus type 1 (HIV-1). Here, the solution structure of the HIV-1 frameshifting RNA signal was solved by heteronuclear NMR spectroscopy. This structure reveals a long hairpin fold with an internal three-nucleotide bulge. The internal loop introduces a bend between the lower and upper helical regions, a structural feature often seen in frameshifting pseudoknots. The NMR structure correlates with chemical probing data. The upper stem rich in conserved G-C Watson-Crick base-pairs is highly stable, whereas the bulge region and the lower stem are more flexible.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Composition*
  • Base Sequence
  • Frameshifting, Ribosomal*
  • HIV-1 / chemistry
  • HIV-1 / genetics*
  • Humans
  • Molecular Sequence Data
  • Nuclear Magnetic Resonance, Biomolecular
  • Nucleic Acid Conformation
  • Protein Biosynthesis*
  • RNA, Viral / chemistry
  • RNA, Viral / genetics*
  • Ribosomes / chemistry
  • Ribosomes / genetics

Substances

  • RNA, Viral

Associated data

  • PDB/1ZC5