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

Cyril Gaudin, Marie-Hélène Mazauric, Mounir Traïkia, Eric Guittet, Satoko Yoshizawa, Dominique Fourmy

Laboratoire de RMN, ICSN-CNRS 1 ave de la terrasse, 91190 Gif-sur-Yvette, France.

Journal of molecular biology 2005 Jun 24

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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.

Citation

Cyril Gaudin, Marie-Hélène Mazauric, Mounir Traïkia, Eric Guittet, Satoko Yoshizawa, Dominique Fourmy. Structure of the RNA signal essential for translational frameshifting in HIV-1. Journal of molecular biology. 2005 Jun 24;349(5):1024-35