title: The highly conserved codon following the slippery sequence supports -1 frameshift efficiency at the HIV-1 frameshift site.
abstract: HIV-1 utilises -1 programmed ribosomal frameshifting to translate structural and enzymatic domains in a defined proportion required for replication. A slippery sequence, U UUU UUA, and a stem-loop are well-defined RNA features modulating -1 frameshifting in HIV-1. The GGG glycine codon immediately following the slippery sequence (the 'intercodon') contributes structurally to the start of the stem-loop but has no defined role in current models of the frameshift mechanism, as slippage is inferred to occur before the intercodon has reached the ribosomal decoding site. This GGG codon is highly conserved in natural isolates of HIV. When the natural intercodon was replaced with a stop codon two different decoding molecules-eRF1 protein or a cognate suppressor tRNA-were able to access and decode the intercodon prior to -1 frameshifting. This implies significant slippage occurs when the intercodon is in the (perhaps distorted) ribosomal A site. We accommodate the influence of the intercodon in a model of frame maintenance versus frameshifting in HIV-1.
authors: Department of Biochemistry, University of Otago, Dunedin, 9054, New Zealand.
authors: Suneeth F
authors: SF
authors: Mathew
authors: Department of Biochemistry, University of Otago, Dunedin, 9054, New Zealand.
authors: Caillan
authors: C
authors: Crowe-McAuliffe
authors: Department of Biochemistry, University of Otago, Dunedin, 9054, New Zealand.
authors: Ryan
authors: R
authors: Graves
authors: Department of Biochemistry, University of Otago, Dunedin, 9054, New Zealand.
authors: Tony S
authors: TS
authors: Cardno
authors: Department of Biochemistry, University of Otago, Dunedin, 9054, New Zealand.
authors: Cushla
authors: C
authors: McKinney
authors: Department of Biochemistry, University of Otago, Dunedin, 9054, New Zealand.
authors: Elizabeth S
authors: ES
authors: Poole
authors: Department of Biochemistry, University of Otago, Dunedin, 9054, New Zealand.
authors: Warren P
authors: WP
authors: Tate
mesh_terms: D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D002522:Chlorocebus aethiops; D003062:Codon; D018965:Frameshifting, Ribosomal; D057809:HEK293 Cells; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D009690:Nucleic Acid Conformation; D010454:Peptide Termination Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D012343:RNA, Transfer / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D003062:Codon; C489002:ETF1 protein, human; D010454:Peptide Termination Factors; D034741:RNA, Small Interfering; D012343:RNA, Transfer