title: Highly conserved RNA pseudoknots at the Gag-Pol junction of HIV-1 suggest a novel mechanism of -1 ribosomal frameshifting.
abstract: -1 programmed ribosomal frameshifting (PRF) is utilized by many viruses to synthesize their enzymatic (Pol) and structural (Gag) proteins at a defined ratio. For efficient -1 PRF, two cis-acting elements are required: a heptanucleotide frameshift site and a downstream stimulator such as a pseudoknot. We have analyzed the gag-pol junction sequences from 4254 HIV-1 strains. Approximately ninety-five percent of the sequences can form four pseudoknots PK1-PK4 (∼ 97% contain PK1, PK3, and PK4), covering ∼ 72 nt including the frameshift site. Some pseudoknots are mutually excluded due to sequence overlap. PK1 and PK3 arrange tandemly. Their stems form a quasi-continuous helix of ∼ 22 bp. We propose a novel mechanism for possible roles of these pseudoknots. Multiple alternative structures may exist at the gag-pol junction. In most strains, the PK1-PK3 tandem pseudoknots may dominate the structurally heterogeneous pool of RNA due to their greater overall stability. The tandem pseudoknots may function as a breaking system to slow down the ribosome. The ribosome unwinds PK1 and stem 1 of PK3 before it can reach the frameshift site. Then, PK4 can form rapidly because the intact stem 2 of PK3 makes up a large part of the stem 1 of PK4. The newly formed PK4 jams the entrance of the mRNA tunnel. The process then proceeds as in a typical case of -1 PRF. This mechanism incorporates several exquisite new features while still being consistent with the current paradigm of pseudoknot-dependent -1 PRF.
authors.forename: Xiaolan
authors.initials: X
authors.lastname: Huang
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.forename: Guan
authors.initials: G
authors.lastname: Wang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Cheng
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Du
mesh_terms: D018965:Frameshifting, Ribosomal / Q000235:genetics*; D015685:Fusion Proteins, gag-pol / Q000235:genetics*; D016679:Genome, Viral; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D009690:Nucleic Acid Conformation; D012367:RNA, Viral / Q000235:genetics*; D012270:Ribosomes / Q000235:genetics
chemical_list: D015685:Fusion Proteins, gag-pol; D012367:RNA, Viral
keywords: -1 ribosomal frameshifting; HIV-1; RNA pseudoknot; recoding