Structure of the RNA Signal Essential for Translational Frameshifting in HIV-1

• Published in: Journal of molecular biology 2005-06, Vol.349 (5), p.1024-1035
• Main Authors: Gaudin, Cyril, Mazauric, Marie-Hélène, Traïkia, Mounir, Guittet, Eric, Yoshizawa, Satoko, Fourmy, Dominique
• Format: Article
• Language: English
• Subjects: Base Composition; Base Sequence; frameshift; Frameshifting, Ribosomal; HIV-1; HIV-1 - chemistry; HIV-1 - genetics; Human immunodeficiency virus 1; Humans; Molecular Sequence Data; mRNA; NMR spectroscopy; Nuclear Magnetic Resonance, Biomolecular; Nucleic Acid Conformation; Protein Biosynthesis; Ribosomes - chemistry; Ribosomes - genetics; RNA, Viral - chemistry; RNA, Viral - genetics; translation
• ISSN: 0022-2836; 1089-8638
• DOI: 10.1016/j.jmb.2005.04.045

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.