An RNA pseudoknot and an optimal heptameric shift site are required for highly efficient ribosomal frameshifting on a retroviral messenger RNA.

Programmed ribosomal frameshifting (PRF) is a conserved translational recoding mechanism found in all branches of life and viruses. In bacteria, archaea, and eukaryotes PRF is used to downregulate protein production by inducing a premature termination of translation, which triggers messenger RNA (mRNA) decay. In viruses, PRF is used to drive the production of a new protein while downregulating the production of another protein, thus maintaining a stoichiometry optimal for productive infection. Traditionally, PRF motifs have been defined by the characteristics of two cis elements: a slippery heptanucleotide sequence followed by an RNA pseudoknot or stem-loop within the mRNA. Recently, additional cis and new trans elements have been identified that regulate PRF in both host and viral translation. These additional factors suggest PRF is an evolutionarily conserved process whose function and regulation we are just beginning to understand.

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An atypical RNA pseudoknot stimulator and an upstream attenuation signal for -1 ribosomal frameshifting of SARS coronavirus

Nucleic Acids Research ◽

10.1093/nar/gki731 ◽

2005 ◽

Vol 33 (13) ◽

pp. 4265-4275 ◽

Cited By ~ 47

Author(s):

M.-C. Su

Keyword(s):

Sars Coronavirus ◽

Ribosomal Frameshifting ◽

Rna Pseudoknot

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Small synthetic molecule-stabilized RNA pseudoknot as an activator for –1 ribosomal frameshifting

Nucleic Acids Research ◽

10.1093/nar/gky689 ◽

2018 ◽

Vol 46 (16) ◽

pp. 8079-8089 ◽

Cited By ~ 8

Author(s):

Saki Matsumoto ◽

Neva Caliskan ◽

Marina V Rodnina ◽

Asako Murata ◽

Kazuhiko Nakatani

Keyword(s):

Ribosomal Frameshifting ◽

Rna Pseudoknot ◽

Synthetic Molecule

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Characterization of an efficient coronavirus ribosomal frameshifting signal: Requirement for an RNA pseudoknot

Cell ◽

10.1016/0092-8674(89)90124-4 ◽

1989 ◽

Vol 57 (4) ◽

pp. 537-547 ◽

Cited By ~ 386

Author(s):

Ian Brierley ◽

Paul Digard ◽

Stephen C. Inglis

Keyword(s):

Ribosomal Frameshifting ◽

Rna Pseudoknot

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Novel Gag-Pol Frameshift Site in Human Immunodeficiency Virus Type 1 Variants Resistant to Protease Inhibitors

Journal of Virology ◽

10.1128/jvi.72.7.6146-6150.1998 ◽

1998 ◽

Vol 72 (7) ◽

pp. 6146-6150 ◽

Cited By ~ 52

Author(s):

Louise Doyon ◽

Catherine Payant ◽

Léa Brakier-Gingras ◽

Daniel Lamarre

Keyword(s):

Human Immunodeficiency Virus ◽

Protease Inhibitors ◽

Human Immunodeficiency Virus Type ◽

Virus Type ◽

Cleavage Site ◽

Messenger Rna ◽

Site Mutation ◽

Ribosomal Frameshifting ◽

Immunodeficiency Virus

ABSTRACT Human immunodeficiency virus type 1 (HIV-1) variants resistant to protease inhibitors have been shown to contain a mutation in the p1/p6 Gag precursor cleavage site. At the messenger RNA level, this mutation generates a U UUU UUU sequence that is reminiscent of the U UUU UUA sequence required for ribosomal frameshifting and Gag-Pol synthesis. To test whether the p1/p6 cleavage site mutation was generating a novel frameshift site, HIV sequences were inserted in translation vectors containing a chloramphenicol acetyltransferase (CAT) reporter gene requiring −1 frameshifting for expression. All sequences containing the original HIV frameshift site supported the synthesis of CAT but expression was increased 3- to 11-fold in the presence of the mutant p1/p6 sequence. When the original frameshift site was abolished by mutation, expression remained unchanged when using constructs containing the mutant p1/p6 sequence, whereas it was decreased 2- to 4.5-fold when using wild-type p1/p6 constructs. Similarly, when introduced into HIV molecular clones, the p1/p6 mutant sequence supported Gag-Pol synthesis and protease activity in the absence of the original frameshift site, indicating that this sequence could also promote ribosomal frameshifting in virus-expressing cells.

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Pseudoknot Structures in Retroviral and Bacteriophage Messenger RNA: a Family of Structurally Related RNA Pseudoknots

Microscopy and Microanalysis ◽

10.1017/s1431927600007364 ◽

1997 ◽

Vol 3 (S2) ◽

pp. 95-96

Author(s):

D.W. Hoffman ◽

Z. Du ◽

J.A. Holland ◽

M.R. Hansen ◽

Y. Wang ◽

...

Keyword(s):

Messenger Rna ◽

Three Dimensional ◽

Structural Features ◽

Dimensional Structure ◽

Three Dimensional Model ◽

Single Nucleotide ◽

Rna Pseudoknots ◽

Gene 32 ◽

Rna Pseudoknot ◽

Bacteriophage T2

Nuclear magnetic resonance (NMR) spectroscopy was used to determine the three-dimensional structure of an RNA pseudoknot with a sequence corresponding to the 5' end region of the gene 32 messenger RNA of bacteriophage T2. NMR results show that the pseudoknot contains two coaxial A-form helical stems connected by two loops. One of the loops consists of a single nucleotide, which spans the major groove of the seven base pair helical stem 2. The second loop consists of 7 nucleotides, and spans the minor groove of stem 1. A three-dimensional model of the pseudoknot that is consistent with the NMR data will be presented, and features that are likely to be important for stabilizing the pseudoknot structure will be described.A combination of NMR and phylogenetic methods were used to characterize the structural features of RNA pseudoknots that are associated with frameshift and readthrough sites within the retroviral gag-pro messenger RNA. The majority of the retroviral frameshift and readthrough sites were found to be followed by nucleotide sequences that have the potential to form pseudoknots with structures that are remarkably similar to that of the bacteriophage T2 gene 32 mRNA.

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