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1

Choi, Jinah, Zhenming Xu, and Jing-hsiung Ou. "Triple Decoding of Hepatitis C Virus RNA by Programmed Translational Frameshifting." Molecular and Cellular Biology 23, no. 5 (2003): 1489–97. http://dx.doi.org/10.1128/mcb.23.5.1489-1497.2003.

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ABSTRACT Ribosomes can be programmed to shift from one reading frame to another during translation. Hepatitis C virus (HCV) uses such a mechanism to produce F protein from the −2/+1 reading frame. We now report that the HCV frameshift signal can mediate the synthesis of the core protein of the zero frame, the F protein of the −2/+1 frame, and a 1.5-kDa protein of the −1/+2 frame. This triple decoding function does not require sequences flanking the frameshift signal and is apparently independent of membranes and the synthesis of the HCV polyprotein. Two consensus −1 frameshift sequences in the
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2

Lopinski, John D., Jonathan D. Dinman, and Jeremy A. Bruenn. "Kinetics of Ribosomal Pausing during Programmed −1 Translational Frameshifting." Molecular and Cellular Biology 20, no. 4 (2000): 1095–103. http://dx.doi.org/10.1128/mcb.20.4.1095-1103.2000.

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ABSTRACT In the Saccharomyces cerevisiae double-stranded RNA virus, programmed −1 ribosomal frameshifting is responsible for translation of the second open reading frame of the essential viral RNA. A typical slippery site and downstream pseudoknot are necessary for this frameshifting event, and previous work has demonstrated that ribosomes pause over the slippery site. The translational intermediate associated with a ribosome paused at this position is detected, and, using in vitro translation and quantitative heelprinting, the rates of synthesis, the ribosomal pause time, the proportion of ri
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3

Schütz, G. M. "On the stationary frequency of programmed ribosomal −1 frameshift." Journal of Statistical Mechanics: Theory and Experiment 2020, no. 4 (2020): 043502. http://dx.doi.org/10.1088/1742-5468/ab7a1d.

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4

Tumer, Nilgun E., Bijal A. Parikh, Ping Li, and Jonathan D. Dinman. "The Pokeweed Antiviral Protein Specifically Inhibits Ty1-Directed +1 Ribosomal Frameshifting and Retrotransposition in Saccharomyces cerevisiae." Journal of Virology 72, no. 2 (1998): 1036–42. http://dx.doi.org/10.1128/jvi.72.2.1036-1042.1998.

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ABSTRACT Programmed ribosomal frameshifting is a molecular mechanism that is used by many RNA viruses to produce Gag-Pol fusion proteins. The efficiency of these frameshift events determines the ratio of viral Gag to Gag-Pol proteins available for viral particle morphogenesis, and changes in ribosomal frameshift efficiencies can severely inhibit virus propagation. Since ribosomal frameshifting occurs during the elongation phase of protein translation, it is reasonable to hypothesize that agents that affect the different steps in this process may also have an impact on programmed ribosomal fram
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5

Garcia-Miranda, Pablo, Jordan T. Becker, Bayleigh E. Benner, Alexander Blume, Nathan M. Sherer, and Samuel E. Butcher. "Stability of HIV Frameshift Site RNA Correlates with Frameshift Efficiency and Decreased Virus Infectivity." Journal of Virology 90, no. 15 (2016): 6906–17. http://dx.doi.org/10.1128/jvi.00149-16.

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ABSTRACTHuman immunodeficiency virus (HIV) replication is strongly dependent upon a programmed ribosomal frameshift. Here we investigate the relationships between the thermodynamic stability of the HIV type 1 (HIV-1) RNA frameshift site stem-loop, frameshift efficiency, and infectivity, using pseudotyped HIV-1 and HEK293T cells. The data reveal a strong correlation between frameshift efficiency and local, but not overall, RNA thermodynamic stability. Mutations that modestly increase the local stability of the frameshift site RNA stem-loop structure increase frameshift efficiency 2-fold to 3-fo
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6

Kontos, Harry, Sawsan Napthine, and Ian Brierley. "Ribosomal Pausing at a Frameshifter RNA Pseudoknot Is Sensitive to Reading Phase but Shows Little Correlation with Frameshift Efficiency." Molecular and Cellular Biology 21, no. 24 (2001): 8657–70. http://dx.doi.org/10.1128/mcb.21.24.8657-8670.2001.

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ABSTRACT Here we investigated ribosomal pausing at sites of programmed −1 ribosomal frameshifting, using translational elongation and ribosome heelprint assays. The site of pausing at the frameshift signal of infectious bronchitis virus (IBV) was determined and was consistent with an RNA pseudoknot-induced pause that placed the ribosomal P- and A-sites over the slippery sequence. Similarly, pausing at the simian retrovirus 1 gag/pol signal, which contains a different kind of frameshifter pseudoknot, also placed the ribosome over the slippery sequence, supporting a role for pausing in frameshif
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7

Larsen, B., N. M. Wills, R. F. Gesteland, and J. F. Atkins. "rRNA-mRNA base pairing stimulates a programmed -1 ribosomal frameshift." Journal of Bacteriology 176, no. 22 (1994): 6842–51. http://dx.doi.org/10.1128/jb.176.22.6842-6851.1994.

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8

Peltz, Stuart W., Amy B. Hammell, Ying Cui, Jason Yasenchak, Lara Puljanowski, and Jonathan D. Dinman. "Ribosomal Protein L3 Mutants Alter Translational Fidelity and Promote Rapid Loss of the Yeast Killer Virus." Molecular and Cellular Biology 19, no. 1 (1999): 384–91. http://dx.doi.org/10.1128/mcb.19.1.384.

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ABSTRACT Programmed −1 ribosomal frameshifting is utilized by a number of RNA viruses as a means of ensuring the correct ratio of viral structural to enzymatic proteins available for viral particle assembly. Altering frameshifting efficiencies upsets this ratio, interfering with virus propagation. We have previously demonstrated that compounds that alter the kinetics of the peptidyl-transfer reaction affect programmed −1 ribosomal frameshift efficiencies and interfere with viral propagation in yeast. Here, the use of a genetic approach lends further support to the hypothesis that alterations a
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9

Choi, Junhong, Sinéad O’Loughlin, John F. Atkins, and Joseph D. Puglisi. "The energy landscape of −1 ribosomal frameshifting." Science Advances 6, no. 1 (2020): eaax6969. http://dx.doi.org/10.1126/sciadv.aax6969.

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Maintenance of translational reading frame ensures the fidelity of information transfer during protein synthesis. Yet, programmed ribosomal frameshifting sequences within the coding region promote a high rate of reading frame change at predetermined sites thus enriching genomic information density. Frameshifting is typically stimulated by the presence of 3′ messenger RNA (mRNA) structures, but how these mRNA structures enhance −1 frameshifting remains debatable. Here, we apply single-molecule and ensemble approaches to formulate a mechanistic model of ribosomal −1 frameshifting. Our model sugg
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10

Türkel, Sezai. "Amino Acid Starvation Enhances Programmed Ribosomal Frameshift in Metavirus Ty3 of Saccharomyces cerevisiae." Advances in Biology 2016 (June 30, 2016): 1–6. http://dx.doi.org/10.1155/2016/1840782.

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Ty3 is a retroviral-like element and propagates with a retroviral-like mechanism within the yeast cells. Ty3 mRNA contains two coding regions, which are GAG3 and POL3. The coding region POL3 is translated as a GAG3-POL3 fusion protein by a +1 programmed frameshift. In this study, it was shown that the Ty3 frameshift frequency is significantly increased by amino acid starvation in a Gcn2p complex dependent manner. When the yeast cells were subjected to amino acid starvation, the frameshift frequency of Ty3 increased more than 2-fold in the wild-type yeast cells, mostly independent of Gcn4p. How
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11

Meskauskas, Arturas, Jennifer L. Baxter, Edward A. Carr, et al. "Delayed rRNA Processing Results in Significant Ribosome Biogenesis and Functional Defects." Molecular and Cellular Biology 23, no. 5 (2003): 1602–13. http://dx.doi.org/10.1128/mcb.23.5.1602-1613.2003.

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ABSTRACT mof6-1 was originally isolated as a recessive mutation in Saccharomyces cerevisiae which promoted increased efficiencies of programmed −1 ribosomal frameshifting and rendered cells unable to maintain the killer virus. Here, we demonstrate that mof6-1 is a unique allele of the histone deacetylase RPD3, that the deacetylase function of Rpd3p is required for controlling wild-type levels of frameshifting and virus maintenance, and that the closest human homolog can fully complement these defects. Loss of the Rpd3p-associated histone deacetylase function, either by mutants of rpd3 or loss
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12

Sun, Yu, Laura Abriola, Rachel O. Niederer, et al. "Restriction of SARS-CoV-2 replication by targeting programmed −1 ribosomal frameshifting." Proceedings of the National Academy of Sciences 118, no. 26 (2021): e2023051118. http://dx.doi.org/10.1073/pnas.2023051118.

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Translation of open reading frame 1b (ORF1b) in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) requires a programmed −1 ribosomal frameshift (−1 PRF) promoted by an RNA pseudoknot. The extent to which SARS-CoV-2 replication may be sensitive to changes in −1 PRF efficiency is currently unknown. Through an unbiased, reporter-based high-throughput compound screen, we identified merafloxacin, a fluoroquinolone antibacterial, as a −1 PRF inhibitor for SARS-CoV-2. Frameshift inhibition by merafloxacin is robust to mutations within the pseudoknot region and is similarly effective on −1
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13

Plant, Ewan P., Rasa Rakauskaitė, Deborah R. Taylor, and Jonathan D. Dinman. "Achieving a Golden Mean: Mechanisms by Which Coronaviruses Ensure Synthesis of the Correct Stoichiometric Ratios of Viral Proteins." Journal of Virology 84, no. 9 (2010): 4330–40. http://dx.doi.org/10.1128/jvi.02480-09.

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ABSTRACT In retroviruses and the double-stranded RNA totiviruses, the efficiency of programmed −1 ribosomal frameshifting is critical for ensuring the proper ratios of upstream-encoded capsid proteins to downstream-encoded replicase enzymes. The genomic organizations of many other frameshifting viruses, including the coronaviruses, are very different, in that their upstream open reading frames encode nonstructural proteins, the frameshift-dependent downstream open reading frames encode enzymes involved in transcription and replication, and their structural proteins are encoded by subgenomic mR
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14

Belew, Ashton T., Nicholas L. Hepler, Jonathan L. Jacobs, and Jonathan D. Dinman. "PRFdb: A database of computationally predicted eukaryotic programmed -1 ribosomal frameshift signals." BMC Genomics 9, no. 1 (2008): 339. http://dx.doi.org/10.1186/1471-2164-9-339.

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15

Hsu, Chiung-Fang, Kai-Chun Chang, Yi-Lan Chen, et al. "Formation of frameshift-stimulating RNA pseudoknots is facilitated by remodeling of their folding intermediates." Nucleic Acids Research 49, no. 12 (2021): 6941–57. http://dx.doi.org/10.1093/nar/gkab512.

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Abstract Programmed –1 ribosomal frameshifting is an essential regulation mechanism of translation in viruses and bacteria. It is stimulated by mRNA structures inside the coding region. As the structure is unfolded repeatedly by consecutive translating ribosomes, whether it can refold properly each time is important in performing its function. By using single-molecule approaches and molecular dynamics simulations, we found that a frameshift-stimulating RNA pseudoknot folds sequentially through its upstream stem S1 and downstream stem S2. In this pathway, S2 folds from the downstream side and t
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16

Dulude, D. "Characterization of the frameshift stimulatory signal controlling a programmed -1 ribosomal frameshift in the human immunodeficiency virus type 1." Nucleic Acids Research 30, no. 23 (2002): 5094–102. http://dx.doi.org/10.1093/nar/gkf657.

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17

Hong, Samuel, S. Sunita, Tatsuya Maehigashi, Eric D. Hoffer, Jack A. Dunkle, and Christine M. Dunham. "Mechanism of tRNA-mediated +1 ribosomal frameshifting." Proceedings of the National Academy of Sciences 115, no. 44 (2018): 11226–31. http://dx.doi.org/10.1073/pnas.1809319115.

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Accurate translation of the genetic code is critical to ensure expression of proteins with correct amino acid sequences. Certain tRNAs can cause a shift out of frame (i.e., frameshifting) due to imbalances in tRNA concentrations, lack of tRNA modifications or insertions or deletions in tRNAs (called frameshift suppressors). Here, we determined the structural basis for how frameshift-suppressor tRNASufA6 (a derivative of tRNAPro) reprograms the mRNA frame to translate a 4-nt codon when bound to the bacterial ribosome. After decoding at the aminoacyl (A) site, the crystal structure of the antico
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18

Napthine, Sawsan, Susanne Bell, Chris H. Hill, Ian Brierley, and Andrew E. Firth. "Characterization of the stimulators of protein-directed ribosomal frameshifting in Theiler's murine encephalomyelitis virus." Nucleic Acids Research 47, no. 15 (2019): 8207–23. http://dx.doi.org/10.1093/nar/gkz503.

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AbstractMany viruses utilize programmed –1 ribosomal frameshifting (–1 PRF) to express additional proteins or to produce frameshift and non-frameshift protein products at a fixed stoichiometric ratio. PRF is also utilized in the expression of a small number of cellular genes. Frameshifting is typically stimulated by signals contained within the mRNA: a ‘slippery’ sequence and a 3′-adjacent RNA structure. Recently, we showed that −1 PRF in encephalomyocarditis virus (EMCV) is trans-activated by the viral 2A protein, leading to a temporal change in PRF efficiency from 0% to 70% during virus infe
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19

Sharma, Virag, Marie-Françoise Prère, Isabelle Canal, et al. "Analysis of tetra- and hepta-nucleotides motifs promoting -1 ribosomal frameshifting in Escherichia coli." Nucleic Acids Research 42, no. 11 (2014): 7210–25. http://dx.doi.org/10.1093/nar/gku386.

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Abstract Programmed ribosomal -1 frameshifting is a non-standard decoding process occurring when ribosomes encounter a signal embedded in the mRNA of certain eukaryotic and prokaryotic genes. This signal has a mandatory component, the frameshift motif: it is either a Z_ZZN tetramer or a X_XXZ_ZZN heptamer (where ZZZ and XXX are three identical nucleotides) allowing cognate or near-cognate repairing to the -1 frame of the A site or A and P sites tRNAs. Depending on the signal, the frameshifting frequency can vary over a wide range, from less than 1% to more than 50%. The present study combines
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20

Girnary, Roseanne, Louise King, Laurence Robinson, Robert Elston, and Ian Brierley. "Structure–function analysis of the ribosomal frameshifting signal of two human immunodeficiency virus type 1 isolates with increased resistance to viral protease inhibitors." Journal of General Virology 88, no. 1 (2007): 226–35. http://dx.doi.org/10.1099/vir.0.82064-0.

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Expression of the pol-encoded proteins of human immunodeficiency virus type 1 (HIV-1) requires a programmed –1 ribosomal frameshift at the junction of the gag and pol coding sequences. Frameshifting takes place at a heptanucleotide slippery sequence, UUUUUUA, and is enhanced by a stimulatory RNA structure located immediately downstream. In patients undergoing viral protease (PR) inhibitor therapy, a p1/p6gag L449F cleavage site (CS) mutation is often observed in resistant isolates and frequently generates, at the nucleotide sequence level, a homopolymeric and potentially slippery sequence (UUU
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21

Plant, E. P. "A programmed -1 ribosomal frameshift signal can function as a cis-acting mRNA destabilizing element." Nucleic Acids Research 32, no. 2 (2004): 784–90. http://dx.doi.org/10.1093/nar/gkh256.

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22

Manktelow, E. "Characterization of the frameshift signal of Edr, a mammalian example of programmed -1 ribosomal frameshifting." Nucleic Acids Research 33, no. 5 (2005): 1553–63. http://dx.doi.org/10.1093/nar/gki299.

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23

Jacobs, Jonathan L., Ashton T. Belew, Rasa Rakauskaite, and Jonathan D. Dinman. "Identification of functional, endogenous programmed −1 ribosomal frameshift signals in the genome of Saccharomyces cerevisiae." Nucleic Acids Research 35, no. 1 (2006): 165–74. http://dx.doi.org/10.1093/nar/gkl1033.

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24

Kelly, Jamie A., Alexandra N. Olson, Krishna Neupane, et al. "Structural and functional conservation of the programmed −1 ribosomal frameshift signal of SARS coronavirus 2 (SARS-CoV-2)." Journal of Biological Chemistry 295, no. 31 (2020): 10741–48. http://dx.doi.org/10.1074/jbc.ac120.013449.

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Approximately 17 years after the severe acute respiratory syndrome coronavirus (SARS-CoV) epidemic, the world is currently facing the COVID-19 pandemic caused by SARS corona virus 2 (SARS-CoV-2). According to the most optimistic projections, it will take more than a year to develop a vaccine, so the best short-term strategy may lie in identifying virus-specific targets for small molecule–based interventions. All coronaviruses utilize a molecular mechanism called programmed −1 ribosomal frameshift (−1 PRF) to control the relative expression of their proteins. Previous analyses of SARS-CoV have
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Huang, Wan-Ping, Che-Pei Cho, and Kung-Yao Chang. "mRNA-Mediated Duplexes Play Dual Roles in the Regulation of Bidirectional Ribosomal Frameshifting." International Journal of Molecular Sciences 19, no. 12 (2018): 3867. http://dx.doi.org/10.3390/ijms19123867.

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In contrast to −1 programmed ribosomal frameshifting (PRF) stimulation by an RNA pseudoknot downstream of frameshifting sites, a refolding upstream RNA hairpin juxtaposing the frameshifting sites attenuates −1 PRF in human cells and stimulates +1 frameshifting in yeast. This eukaryotic functional mimicry of the internal Shine-Dalgarno (SD) sequence-mediated duplex was confirmed directly in the 70S translation system, indicating that both frameshifting regulation activities of upstream hairpin are conserved between 70S and 80S ribosomes. Unexpectedly, a downstream pseudoknot also possessed two
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26

Finch, Leanne K., Roger Ling, Sawsan Napthine, et al. "Characterization of Ribosomal Frameshifting in Theiler's Murine Encephalomyelitis Virus." Journal of Virology 89, no. 16 (2015): 8580–89. http://dx.doi.org/10.1128/jvi.01043-15.

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ABSTRACTTheiler's murine encephalomyelitis virus(TMEV) is a member of the genusCardiovirusin thePicornaviridae, a family of positive-sense single-stranded RNA viruses. Previously, we demonstrated that in the related cardiovirus,Encephalomyocarditis virus, a programmed −1 ribosomal frameshift (−1 PRF) occurs at a conserved G_GUU_UUU sequence within the 2B-encoding region of the polyprotein open reading frame (ORF). Here we show that −1 PRF occurs at a similar site during translation of the TMEV genome. In addition, we demonstrate that a predicted 3′ RNA stem-loop structure at a noncanonical spa
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27

Wan, Ji, Xiangwei Gao, Yuanhui Mao, Xingqian Zhang, and Shu-Bing Qian. "A Coding Sequence-Embedded Principle Governs Translational Reading Frame Fidelity." Research 2018 (September 20, 2018): 1–15. http://dx.doi.org/10.1155/2018/7089174.

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Upon initiation at a start codon, the ribosome must maintain the correct reading frame for hundreds of codons in order to produce functional proteins. While some sequence elements are able to trigger programmed ribosomal frameshifting (PRF), very little is known about how the ribosome normally prevents spontaneous frameshift errors that can have dire consequences if uncorrected. Using high resolution ribosome profiling data sets, we discovered that the translating ribosome uses the 3′ end of 18S rRNA to scan the AUG-like codons after the decoding process. The postdecoding mRNA:rRNA interaction
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28

Lawler, Joseph F., Gennady V. Merkulov, and Jef D. Boeke. "Frameshift Signal Transplantation and the Unambiguous Analysis of Mutations in the Yeast Retrotransposon Ty1 Gag-Pol Overlap Region." Journal of Virology 75, no. 15 (2001): 6769–75. http://dx.doi.org/10.1128/jvi.75.15.6769-6775.2001.

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ABSTRACT The yeast retrotransposon Ty1 encodes a 7-nucleotide RNA sequence that directs a programmed, +1 ribosomal frameshifting event required for Gag-Pol translation and retrotransposition. We report mutations that block frameshifting, which can be suppressed in cisby “transplanting” the frameshift signal to a position upstream of its native location. These “frameshift transplant” mutants transpose with only a modest decrease in efficiency, suggesting that the location of the frameshift signal in a functional Ty1 element may vary. The genomic architecture of Ty1 is such that Gag, Ty1 PR (PR)
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29

Halma, Matthew T. J., Dustin B. Ritchie, Tonia R. Cappellano, Krishna Neupane, and Michael T. Woodside. "Complex dynamics under tension in a high-efficiency frameshift stimulatory structure." Proceedings of the National Academy of Sciences 116, no. 39 (2019): 19500–19505. http://dx.doi.org/10.1073/pnas.1905258116.

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Specific structures in mRNA can stimulate programmed ribosomal frameshifting (PRF). PRF efficiency can vary enormously between different stimulatory structures, but the features that lead to efficient PRF stimulation remain uncertain. To address this question, we studied the structural dynamics of the frameshift signal from West Nile virus (WNV), which stimulates −1 PRF at very high levels and has been proposed to form several different structures, including mutually incompatible pseudoknots and a double hairpin. Using optical tweezers to apply tension to single mRNA molecules, mimicking the t
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30

Firth, A. E., B. W. Jagger, H. M. Wise, et al. "Ribosomal frameshifting used in influenza A virus expression occurs within the sequence UCC_UUU_CGU and is in the +1 direction." Open Biology 2, no. 10 (2012): 120109. http://dx.doi.org/10.1098/rsob.120109.

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Programmed ribosomal frameshifting is used in the expression of many virus genes and some cellular genes. In eukaryotic systems, the most well-characterized mechanism involves –1 tandem tRNA slippage on an X_XXY_YYZ motif. By contrast, the mechanisms involved in programmed +1 (or −2) slippage are more varied and often poorly characterized. Recently, a novel gene, PA-X, was discovered in influenza A virus and found to be expressed via a shift to the +1 reading frame. Here, we identify, by mass spectrometric analysis, both the site (UCC_UUU_CGU) and direction (+1) of the frameshifting that is in
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31

BARIL, M. "Efficiency of a programmed -1 ribosomal frameshift in the different subtypes of the human immunodeficiency virus type 1 group M." RNA 9, no. 10 (2003): 1246–53. http://dx.doi.org/10.1261/rna.5113603.

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32

Atkins, John F., and Glenn R. Björk. "A Gripping Tale of Ribosomal Frameshifting: Extragenic Suppressors of Frameshift Mutations Spotlight P-Site Realignment." Microbiology and Molecular Biology Reviews 73, no. 1 (2009): 178–210. http://dx.doi.org/10.1128/mmbr.00010-08.

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SUMMARYMutants of translation components which compensate for both −1 and +1 frameshift mutations showed the first evidence for framing malleability. Those compensatory mutants isolated in bacteria and yeast with altered tRNA or protein factors are reviewed here and are considered to primarily cause altered P-site realignment and not altered translocation. Though the first sequenced tRNA mutant which suppressed a +1 frameshift mutation had an extra base in its anticodon loop and led to a textbook “yardstick” model in which the number of anticodon bases determines codon size, this model has lon
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33

Leger, M., D. Dulude, S. V. Steinberg, and L. Brakier-Gingras. "The three transfer RNAs occupying the A, P and E sites on the ribosome are involved in viral programmed -1 ribosomal frameshift." Nucleic Acids Research 35, no. 16 (2007): 5581–92. http://dx.doi.org/10.1093/nar/gkm578.

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34

Huang, Xiaolan, Qiang Cheng, and Zhihua Du. "A Genome-Wide Analysis of RNA Pseudoknots That Stimulate Efficient −1 Ribosomal Frameshifting or Readthrough in Animal Viruses." BioMed Research International 2013 (2013): 1–15. http://dx.doi.org/10.1155/2013/984028.

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Programmed −1 ribosomal frameshifting (PRF) and stop codon readthrough are two translational recoding mechanisms utilized by some RNA viruses to express their structural and enzymatic proteins at a defined ratio. Efficient recoding usually requires an RNA pseudoknot located several nucleotides downstream from the recoding site. To assess the strategic importance of the recoding pseudoknots, we have carried out a large scale genome-wide analysis in which we used an in-house developed program to detect all possible H-type pseudoknots within the genomic mRNAs of 81 animal viruses. Pseudoknots are
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35

Patel, Ankoor, Emmely E. Treffers, Markus Meier, et al. "Molecular characterization of the RNA-protein complex directing −2/−1 programmed ribosomal frameshifting during arterivirus replicase expression." Journal of Biological Chemistry 295, no. 52 (2020): 17904–21. http://dx.doi.org/10.1074/jbc.ra120.016105.

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Programmed ribosomal frameshifting (PRF) is a mechanism used by arteriviruses like porcine reproductive and respiratory syndrome virus (PRRSV) to generate multiple proteins from overlapping reading frames within its RNA genome. PRRSV employs −1 PRF directed by RNA secondary and tertiary structures within its viral genome (canonical PRF), as well as a noncanonical −1 and −2 PRF that are stimulated by the interactions of PRRSV nonstructural protein 1β (nsp1β) and host protein poly(C)-binding protein (PCBP) 1 or 2 with the viral genome. Together, nsp1β and one of the PCBPs act as transactivators
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36

Mishra, Bhavya, and Debashish Chowdhury. "Programmed −1 Frameshift of a Ribosome: Non-Monotonic Variation of Frameshift Efficiency with Increasing Stiffness of mRNA Secondary Structure." Biophysical Journal 110, no. 3 (2016): 234a. http://dx.doi.org/10.1016/j.bpj.2015.11.1292.

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37

Pande, S., A. Vimaladithan, H. Zhao, and P. J. Farabaugh. "Pulling the ribosome out of frame by +1 at a programmed frameshift site by cognate binding of aminoacyl-tRNA." Molecular and Cellular Biology 15, no. 1 (1995): 298–304. http://dx.doi.org/10.1128/mcb.15.1.298.

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Programmed translational frameshifts efficiently alter a translational reading frame by shifting the reading frame during translation. A +1 frameshift has two simultaneous requirements: a translational pause which occurs when either an inefficiently recognized sense or termination codon occupies the A site, and the presence of a special peptidyl-tRNA occupying the P site during the pause. The special nature of the peptidyl-tRNA reflects its ability to slip +1 on the mRNA or to facilitate binding of an incoming aminoacyl-tRNA out of frame in the A site. This second mechanism suggested that in s
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38

Vimaladithan, A., and P. J. Farabaugh. "Special peptidyl-tRNA molecules can promote translational frameshifting without slippage." Molecular and Cellular Biology 14, no. 12 (1994): 8107–16. http://dx.doi.org/10.1128/mcb.14.12.8107.

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Recently we described an unusual programmed +1 frameshift event in yeast retrotransposon Ty3. Frameshifting depends on the presence of peptidyl-tRNA(AlaCGC) on the GCG codon in the ribosomal P site and on a translational pause stimulated by the slowly decoded AGU codon. Frameshifting occurs on the sequence GCG-AGU-U by out-of-frame binding of a valyl-tRNA to GUU without slippage of peptidyl-tRNA(AlaCGC). This mechanism challenges the conventional understanding that frameshift efficiency must correlate with the ability of mRNA-bound tRNA to slip between cognate or near-cognate codons. Though fr
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Vimaladithan, A., and P. J. Farabaugh. "Special peptidyl-tRNA molecules can promote translational frameshifting without slippage." Molecular and Cellular Biology 14, no. 12 (1994): 8107–16. http://dx.doi.org/10.1128/mcb.14.12.8107-8116.1994.

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Recently we described an unusual programmed +1 frameshift event in yeast retrotransposon Ty3. Frameshifting depends on the presence of peptidyl-tRNA(AlaCGC) on the GCG codon in the ribosomal P site and on a translational pause stimulated by the slowly decoded AGU codon. Frameshifting occurs on the sequence GCG-AGU-U by out-of-frame binding of a valyl-tRNA to GUU without slippage of peptidyl-tRNA(AlaCGC). This mechanism challenges the conventional understanding that frameshift efficiency must correlate with the ability of mRNA-bound tRNA to slip between cognate or near-cognate codons. Though fr
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40

Ramsay, Joshua P., Laura G. L. Tester, Anthony S. Major, et al. "Ribosomal frameshifting and dual-target antiactivation restrict quorum-sensing–activated transfer of a mobile genetic element." Proceedings of the National Academy of Sciences 112, no. 13 (2015): 4104–9. http://dx.doi.org/10.1073/pnas.1501574112.

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Symbiosis islands are integrative and conjugative mobile genetic elements that convert nonsymbiotic rhizobia into nitrogen-fixing symbionts of leguminous plants. Excision of the Mesorhizobium loti symbiosis island ICEMlSymR7A is indirectly activated by quorum sensing through TraR-dependent activation of the excisionase gene rdfS. Here we show that a +1 programmed ribosomal frameshift (PRF) fuses the coding sequences of two TraR-activated genes, msi172 and msi171, producing an activator of rdfS expression named Frameshifted excision activator (FseA). Mass-spectrometry and mutational analyses in
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Omar, Sara Ibrahim, Meng Zhao, Rohith Vedhthaanth Sekar, Sahar Arbabi Moghadam, Jack A. Tuszynski, and Michael T. Woodside. "Modeling the structure of the frameshift-stimulatory pseudoknot in SARS-CoV-2 reveals multiple possible conformers." PLOS Computational Biology 17, no. 1 (2021): e1008603. http://dx.doi.org/10.1371/journal.pcbi.1008603.

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The coronavirus causing the COVID-19 pandemic, SARS-CoV-2, uses −1 programmed ribosomal frameshifting (−1 PRF) to control the relative expression of viral proteins. As modulating −1 PRF can inhibit viral replication, the RNA pseudoknot stimulating −1 PRF may be a fruitful target for therapeutics treating COVID-19. We modeled the unusual 3-stem structure of the stimulatory pseudoknot of SARS-CoV-2 computationally, using multiple blind structural prediction tools followed by μs-long molecular dynamics simulations. The results were compared for consistency with nuclease-protection assays and sing
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Charbonneau, J., K. Gendron, G. Ferbeyre, and L. Brakier-Gingras. "The 5' UTR of HIV-1 full-length mRNA and the Tat viral protein modulate the programmed -1 ribosomal frameshift that generates HIV-1 enzymes." RNA 18, no. 3 (2012): 519–29. http://dx.doi.org/10.1261/rna.030346.111.

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Gendron, Karine, Johanie Charbonneau, Dominic Dulude, Nikolaus Heveker, Gerardo Ferbeyre, and Léa Brakier-Gingras. "The presence of the TAR RNA structure alters the programmed -1 ribosomal frameshift efficiency of the human immunodeficiency virus type 1 (HIV-1) by modifying the rate of translation initiation." Nucleic Acids Research 36, no. 1 (2007): 30–40. http://dx.doi.org/10.1093/nar/gkm906.

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Niu, Shengniao, Shishu Cao, and Sek-Man Wong. "An infectious RNA with a hepta-adenosine stretch responsible for programmed −1 ribosomal frameshift derived from a full-length cDNA clone of Hibiscus latent Singapore virus." Virology 449 (January 2014): 229–34. http://dx.doi.org/10.1016/j.virol.2013.11.021.

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Ahn, Dae-Gyun, Gun Young Yoon, Sunhee Lee, et al. "A Novel Frameshifting Inhibitor Having Antiviral Activity against Zoonotic Coronaviruses." Viruses 13, no. 8 (2021): 1639. http://dx.doi.org/10.3390/v13081639.

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Recent outbreaks of zoonotic coronaviruses, such as Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), have caused tremendous casualties and great economic shock. Although some repurposed drugs have shown potential therapeutic efficacy in clinical trials, specific therapeutic agents targeting coronaviruses have not yet been developed. During coronavirus replication, a replicase gene cluster, including RNA-dependent RNA polymerase (RdRp), is alternatively translated via a process called -1 programmed ribosomal frameshift (−1
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Sipley, J., and E. Goldman. "Increased ribosomal accuracy increases a programmed translational frameshift in Escherichia coli." Proceedings of the National Academy of Sciences 90, no. 6 (1993): 2315–19. http://dx.doi.org/10.1073/pnas.90.6.2315.

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Theis, Corinna, Jens Reeder, and Robert Giegerich. "KnotInFrame: prediction of −1 ribosomal frameshift events." Nucleic Acids Research 36, no. 18 (2008): 6013–20. http://dx.doi.org/10.1093/nar/gkn578.

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Li, Lei, Alice L. Wang, and Ching C. Wang. "Structural Analysis of the −1 Ribosomal Frameshift Elements in Giardiavirus mRNA." Journal of Virology 75, no. 22 (2001): 10612–22. http://dx.doi.org/10.1128/jvi.75.22.10612-10622.2001.

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ABSTRACT The RNA polymerase of giardiavirus (GLV) is synthesized as a fusion protein through a −1 ribosomal frameshift in a region wheregag and pol open reading frames (ORFs) overlap. A heptamer, CCCUUUA, and a potential pseudoknot found in the overlap were predicted to be required for the frameshift. A 68-nucleotide (nt) cDNA fragment containing these elements was inserted between the GLV 5′ 631-nt cDNA and the out-of-frame luciferase gene that required a −1 frameshift within the 68-nt fragment for expression. Giardia lamblia trophozoites transfected with the transcript of this construct show
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Persson, Britt C., and John F. Atkins. "Does Disparate Occurrence of Autoregulatory Programmed Frameshifting in Decoding the Release Factor 2 Gene Reflect an Ancient Origin with Loss in Independent Lineages?" Journal of Bacteriology 180, no. 13 (1998): 3462–66. http://dx.doi.org/10.1128/jb.180.13.3462-3466.1998.

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ABSTRACT In Escherichia coli an autoregulatory mechanism of programmed ribosomal frameshifting governs the level of polypeptide chain release factor 2. From an analysis of 20 sequences of genes encoding release factor 2, we infer that this frameshift mechanism was present in a common ancestor of a large group of bacteria and has subsequently been lost in three independent lineages.
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Blinkova, A., M. F. Burkart, T. D. Owens, and J. R. Walker. "Conservation of the Escherichia coli dnaX programmed ribosomal frameshift signal in Salmonella typhimurium." Journal of bacteriology 179, no. 13 (1997): 4438–42. http://dx.doi.org/10.1128/jb.179.13.4438-4442.1997.

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