ribosomal frameshifting

Summary

Summary: A directed change in translational READING FRAMES that allows the production of a single protein from two or more OVERLAPPING GENES. The process is programmed by the nucleotide sequence of the MRNA and is sometimes also affected by the secondary or tertiary mRNA structure. It has been described mainly in VIRUSES (especially RETROVIRUSES); RETROTRANSPOSONS; and bacterial insertion elements but also in some cellular genes.

Top Publications

  1. Melian E, Hinzman E, Nagasaki T, Firth A, Wills N, Nouwens A, et al. NS1' of flaviviruses in the Japanese encephalitis virus serogroup is a product of ribosomal frameshifting and plays a role in viral neuroinvasiveness. J Virol. 2010;84:1641-7 pubmed publisher
    ..Using site-directed mutagenesis of these sequence elements in an infectious clone of the Kunjin subtype of West Nile virus, we demonstrate that NS1' plays a role in viral neuroinvasiveness...
  2. Staple D, Butcher S. Solution structure and thermodynamic investigation of the HIV-1 frameshift inducing element. J Mol Biol. 2005;349:1011-23 pubmed
    ..The lower helix must denature to allow the ribosome access to the slippery site, but likely functions as a positioning element that enhances frameshift efficiency. ..
  3. Toulouse A, Au Yeung F, Gaspar C, Roussel J, Dion P, Rouleau G. Ribosomal frameshifting on MJD-1 transcripts with long CAG tracts. Hum Mol Genet. 2005;14:2649-60 pubmed
    ..We show that this phenomenon results from ribosomal slippage to the -1 frame exclusively, that ribosomal frameshifting depends on the presence of long CAG tracts and that polyalanine-frameshifted proteins may enhance ..
  4. Nixon P, Cornish P, Suram S, Giedroc D. Thermodynamic analysis of conserved loop-stem interactions in P1-P2 frameshifting RNA pseudoknots from plant Luteoviridae. Biochemistry. 2002;41:10665-74 pubmed
    ..mRNA pseudoknotted motif overlapping the P1 and P2 open reading frames required for programmed -1 mRNA ribosomal frameshifting. The relationship between structure, stability, and function is poorly understood in these RNA systems...
  5. Barry J, Miller W. A -1 ribosomal frameshift element that requires base pairing across four kilobases suggests a mechanism of regulating ribosome and replicase traffic on a viral RNA. Proc Natl Acad Sci U S A. 2002;99:11133-8 pubmed
    Programmed -1 ribosomal frameshifting is necessary for translation of the polymerase genes of many viruses...
  6. Ivanov I, Atkins J. Ribosomal frameshifting in decoding antizyme mRNAs from yeast and protists to humans: close to 300 cases reveal remarkable diversity despite underlying conservation. Nucleic Acids Res. 2007;35:1842-58 pubmed
    ..The ribosomal frameshifting is a sensor and effector of an autoregulatory circuit which is conserved in animals, fungi and protists...
  7. Girnary R, King L, Robinson L, Elston R, Brierley I. Structure-function analysis of the ribosomal frameshifting signal of two human immunodeficiency virus type 1 isolates with increased resistance to viral protease inhibitors. J Gen Virol. 2007;88:226-35 pubmed
    ..Thus the increased resistance to viral protease inhibitors seen with HIV-1 isolates containing mutations in the frameshifting signal is unlikely to be accounted for solely by enhancement of frameshift efficiency. ..
  8. Henderson C, Anderson C, Howard M. Antisense-induced ribosomal frameshifting. Nucleic Acids Res. 2006;34:4302-10 pubmed
    Programmed ribosomal frameshifting provides a mechanism to decode information located in two overlapping reading frames by diverting a proportion of translating ribosomes into a second open reading frame (ORF)...
  9. Bekaert M, Atkins J, Baranov P. ARFA: a program for annotating bacterial release factor genes, including prediction of programmed ribosomal frameshifting. Bioinformatics. 2006;22:2463-5 pubmed
    ..genes encoding release factors in bacterial genomes is often complicated by utilization of +1 programmed ribosomal frameshifting during synthesis of release factor 2, RF2...

More Information

Publications62

  1. Namy O, Moran S, Stuart D, Gilbert R, Brierley I. A mechanical explanation of RNA pseudoknot function in programmed ribosomal frameshifting. Nature. 2006;441:244-7 pubmed
    ..However, in programmed -1 ribosomal frameshifting, a specific subversion of frame maintenance takes place, wherein the ribosome is forced to shift one ..
  2. Klobutcher L. Sequencing of random Euplotes crassus macronuclear genes supports a high frequency of +1 translational frameshifting. Eukaryot Cell. 2005;4:2098-105 pubmed
    ..crassus is between 3.7% and 31.7% (at a 95% confidence interval). The current and past data also indicate that frameshift sites are found predominantly in genes that likely encode nonabundant proteins in the cell...
  3. Meskauskas A, Petrov A, Dinman J. Identification of functionally important amino acids of ribosomal protein L3 by saturation mutagenesis. Mol Cell Biol. 2005;25:10863-74 pubmed
    ..were genetically characterized with regard to their effects on killer virus maintenance, programmed -1 ribosomal frameshifting, resistance/hypersensitivity to the translational inhibitor anisomycin and, in specific cases, the ..
  4. Firth A, Chung B, Fleeton M, Atkins J. Discovery of frameshifting in Alphavirus 6K resolves a 20-year enigma. Virol J. 2008;5:108 pubmed publisher
    ..The results have implications for alphavirus biology, virion structure, viroporins, ribosomal frameshifting, and bioinformatic identification of novel frameshift-expressed genes, both in viruses and in cellular ..
  5. Atkins J, Bjork G. A gripping tale of ribosomal frameshifting: extragenic suppressors of frameshift mutations spotlight P-site realignment. Microbiol Mol Biol Rev. 2009;73:178-210 pubmed publisher
    ..Their study is revealing how mRNA slippage is restrained except where it is programmed to occur and be utilized. ..
  6. Tamm T, Suurv li J, Lucchesi J, Olspert A, Truve E. Stem-loop structure of Cocksfoot mottle virus RNA is indispensable for programmed -1 ribosomal frameshifting. Virus Res. 2009;146:73-80 pubmed publisher
    The -1 programmed ribosomal frameshifting (-1 PRF) mechanism utilized by many viruses is dependent on a heptanucleotide slippery sequence and a downstream secondary structure element...
  7. Su M, Chang C, Chu C, Tsai C, Chang K. An atypical RNA pseudoknot stimulator and an upstream attenuation signal for -1 ribosomal frameshifting of SARS coronavirus. Nucleic Acids Res. 2005;33:4265-75 pubmed
    The -1 ribosomal frameshifting requires the existence of an in cis RNA slippery sequence and is promoted by a downstream stimulator RNA...
  8. Kobayashi Y, Zhuang J, PELTZ S, Dougherty J. Identification of a cellular factor that modulates HIV-1 programmed ribosomal frameshifting. J Biol Chem. 2010;285:19776-84 pubmed publisher
    Programmed -1 ribosomal frameshifting (PRF) is a distinctive mode of gene expression utilized by some viruses, including human immunodeficiency virus type 1 (HIV-1), to produce multiple proteins from a single mRNA...
  9. Rettberg C, Prere M, Gesteland R, Atkins J, Fayet O. A three-way junction and constituent stem-loops as the stimulator for programmed -1 frameshifting in bacterial insertion sequence IS911. J Mol Biol. 1999;286:1365-78 pubmed
    ..Structural probing and thermal melting profiles indicate that the disrupted three-way junctions have altered structures. ..
  10. Baranov P, Gesteland R, Atkins J. Release factor 2 frameshifting sites in different bacteria. EMBO Rep. 2002;3:373-7 pubmed
    ..Internal translation initiation occurs at the shift site, but any functional role is obscure. ..
  11. Wang Y, Wills N, Du Z, Rangan A, Atkins J, Gesteland R, et al. Comparative studies of frameshifting and nonframeshifting RNA pseudoknots: a mutational and NMR investigation of pseudoknots derived from the bacteriophage T2 gene 32 mRNA and the retroviral gag-pro frameshift site. RNA. 2002;8:981-96 pubmed
  12. Muldoon Jacobs K, Dinman J. Specific effects of ribosome-tethered molecular chaperones on programmed -1 ribosomal frameshifting. Eukaryot Cell. 2006;5:762-70 pubmed
    ..consequences of deletion of either RAC or Ssb1p/2p, experiments relating to cell growth and programmed ribosomal frameshifting (PRF) were assayed...
  13. Dinman J, Ruiz Echevarria M, Czaplinski K, Peltz S. Peptidyl-transferase inhibitors have antiviral properties by altering programmed -1 ribosomal frameshifting efficiencies: development of model systems. Proc Natl Acad Sci U S A. 1997;94:6606-11 pubmed
    The effects of two peptidyl-transferase inhibitors, anisomycin and sparsomycin, on ribosomal frameshifting efficiencies and the propagation of yeast double-stranded RNA viruses were examined...
  14. Firth A, Blitvich B, Wills N, Miller C, Atkins J. Evidence for ribosomal frameshifting and a novel overlapping gene in the genomes of insect-specific flaviviruses. Virology. 2010;399:153-166 pubmed publisher
    ..sequence in the -1/+2 reading frame and is most likely expressed as a trans-frame fusion protein via ribosomal frameshifting at a conserved GGAUUUY slippery heptanucleotide with 3'-adjacent RNA secondary structure (which ..
  15. Liao P, Gupta P, Petrov A, Dinman J, Lee K. A new kinetic model reveals the synergistic effect of E-, P- and A-sites on +1 ribosomal frameshifting. Nucleic Acids Res. 2008;36:2619-29 pubmed publisher
    Programmed ribosomal frameshifting (PRF) is a process by which ribosomes produce two different polypeptides from the same mRNA...
  16. L├ęger M, Dulude D, Steinberg S, Brakier Gingras L. The three transfer RNAs occupying the A, P and E sites on the ribosome are involved in viral programmed -1 ribosomal frameshift. Nucleic Acids Res. 2007;35:5581-92 pubmed
    ..We propose a novel model where -1 PRF is triggered by an incomplete translocation and depends not only on the tRNAs interacting with the P- and A-site codons, but also on the tRNA occupying the E site. ..
  17. Xu Z, Choi J, Yen T, Lu W, Strohecker A, Govindarajan S, et al. Synthesis of a novel hepatitis C virus protein by ribosomal frameshift. EMBO J. 2001;20:3840-8 pubmed
    ..This unexpected finding may open new avenues for the development of anti-HCV drugs. ..
  18. Paul C, Barry J, Dinesh Kumar S, Brault V, Miller W. A sequence required for -1 ribosomal frameshifting located four kilobases downstream of the frameshift site. J Mol Biol. 2001;310:987-99 pubmed
    Programmed ribosomal frameshifting allows one mRNA to encode regulate expression of, multiple open reading frames (ORFs)...
  19. Shigemoto K, Brennan J, Walls E, Watson C, Stott D, Rigby P, et al. Identification and characterisation of a developmentally regulated mammalian gene that utilises -1 programmed ribosomal frameshifting. Nucleic Acids Res. 2001;29:4079-88 pubmed
  20. Kim S, Choi J, Park M, Jeong S, Han K, Kim H. Identification of the +1 ribosomal frameshifting site of LRV1-4 by mutational analysis. Arch Pharm Res. 2005;28:956-62 pubmed
    ..These results indicate that the frameshift site in LRV1-4's is in the 71bp region where ORF2 and ORF3 overlap, and that nt. 2644-2659 (the upward hairpin stem) play a key role in generating the +1 frameshift...
  21. Harger J, Dinman J. An in vivo dual-luciferase assay system for studying translational recoding in the yeast Saccharomyces cerevisiae. RNA. 2003;9:1019-24 pubmed
    ..The assay system has been applied to HIV-1 and L-A directed programmed -1 frameshifting and Ty1 and Ty3 directed +1 frameshifting. The assay system is amenable to high-throughput screening. ..
  22. Plant E, Wang P, Jacobs J, Dinman J. A programmed -1 ribosomal frameshift signal can function as a cis-acting mRNA destabilizing element. Nucleic Acids Res. 2004;32:784-90 pubmed
    ..Analysis of the mRNA decay profiles of the frameshift-signal- containing reporter mRNAs also supports the notion that NMD remains active on mRNAs beyond the 'pioneer round' of translation in yeast. ..
  23. Wang X, Wong S, Liu D. Identification of Hepta- and Octo-Uridine stretches as sole signals for programmed +1 and -1 ribosomal frameshifting during translation of SARS-CoV ORF 3a variants. Nucleic Acids Res. 2006;34:1250-60 pubmed
    ..report the identification of hepta- and octo-uridine stretches as sole signals for programmed +1 and -1 ribosomal frameshifting during translation of severe acute respiratory syndrome coronavirus (SARS-CoV) ORF 3a variants...
  24. Green L, Kim C, Bustamante C, Tinoco I. Characterization of the mechanical unfolding of RNA pseudoknots. J Mol Biol. 2008;375:511-28 pubmed
    ..RNA pseudoknots are also of interest because of their key role in the control of ribosomal frameshifting by viral RNAs...
  25. Baril M, Dulude D, Steinberg S, Brakier Gingras L. The frameshift stimulatory signal of human immunodeficiency virus type 1 group O is a pseudoknot. J Mol Biol. 2003;331:571-83 pubmed
    ..The difference between the frameshift stimulatory signal of group O and group M supports the hypothesis that these groups originate from a different monkey to human transmission. ..
  26. Jacobs J, Belew A, Rakauskaite R, Dinman J. Identification of functional, endogenous programmed -1 ribosomal frameshift signals in the genome of Saccharomyces cerevisiae. Nucleic Acids Res. 2007;35:165-74 pubmed
    In viruses, programmed -1 ribosomal frameshifting (-1 PRF) signals direct the translation of alternative proteins from a single mRNA...
  27. Firth A, Atkins J. A conserved predicted pseudoknot in the NS2A-encoding sequence of West Nile and Japanese encephalitis flaviviruses suggests NS1' may derive from ribosomal frameshifting. Virol J. 2009;6:14 pubmed publisher
    ..by a conserved slippery heptanucleotide (Y CCU UUU), thus forming a classical stimulatory motif for -1 ribosomal frameshifting. We hypothesize, therefore, that the functional importance of the pseudoknot is to stimulate a portion of ..
  28. Napthine S, Vidakovic M, Girnary R, Namy O, Brierley I. Prokaryotic-style frameshifting in a plant translation system: conservation of an unusual single-tRNA slippage event. EMBO J. 2003;22:3941-50 pubmed
    b>Ribosomal frameshifting signals are found in mobile genetic elements, viruses and cellular genes of prokaryotes and eukaryotes...
  29. Petros L, Howard M, Gesteland R, Atkins J. Polyamine sensing during antizyme mRNA programmed frameshifting. Biochem Biophys Res Commun. 2005;338:1478-89 pubmed
    ..We also demonstrate that polyamines are required to stimulate stop codon readthrough at the MuLV redefinition site required for normal expression of the GagPol precursor protein. ..
  30. Roussel J, Pillez A, Montpellier C, Duverlie G, Cahour A, Dubuisson J, et al. Characterization of the expression of the hepatitis C virus F protein. J Gen Virol. 2003;84:1751-9 pubmed
    ..The F protein was tagged with firefly luciferase or the Myc epitope to facilitate its identification. Ribosomal frameshifting was dependent on the presence of mutations in the capsid-encoding sequence...
  31. Mejlhede N, Atkins J, Neuhard J. Ribosomal -1 frameshifting during decoding of Bacillus subtilis cdd occurs at the sequence CGA AAG. J Bacteriol. 1999;181:2930-7 pubmed
    ..The possible function of this frameshift in gene expression is discussed. ..
  32. Sung D, Kang H. Prokaryotic and eukaryotic translational machineries respond differently to the frameshifting RNA signal from plant or animal virus. Virus Res. 2003;92:165-70 pubmed
    ..These results supports the hypothesis that frameshifting occurs by a specific interaction between ribosome and frameshifting signal. ..
  33. Belew A, Hepler N, Jacobs J, Dinman J. PRFdb: a database of computationally predicted eukaryotic programmed -1 ribosomal frameshift signals. BMC Genomics. 2008;9:339 pubmed publisher
    ..It is available on the web at http://dinmanlab.umd.edu/prfdb. ..
  34. Michiels P, Versleijen A, Verlaan P, Pleij C, Hilbers C, Heus H. Solution structure of the pseudoknot of SRV-1 RNA, involved in ribosomal frameshifting. J Mol Biol. 2001;310:1109-23 pubmed
    ..SRV-1) a pseudoknot together with a heptanucleotide slippery sequence are responsible for programmed ribosomal frameshifting, a translational recoding mechanism used to control expression of the Gag-Pol polyprotein from ..
  35. Howard M, Gesteland R, Atkins J. Efficient stimulation of site-specific ribosome frameshifting by antisense oligonucleotides. RNA. 2004;10:1653-61 pubmed
    ..The implications for the mechanism of action of natural programmed translational frameshift stimulators are discussed...
  36. Pallan P, Marshall W, Harp J, Jewett F, Wawrzak Z, Brown B, et al. Crystal structure of a luteoviral RNA pseudoknot and model for a minimal ribosomal frameshifting motif. Biochemistry. 2005;44:11315-22 pubmed
    To understand the role of structural elements of RNA pseudoknots in controlling the extent of -1-type ribosomal frameshifting, we determined the crystal structure of a high-efficiency frameshifting mutant of the pseudoknot from potato ..
  37. Hudak K, Hammell A, Yasenchak J, Tumer N, Dinman J. A C-terminal deletion mutant of pokeweed antiviral protein inhibits programmed +1 ribosomal frameshifting and Ty1 retrotransposition without depurinating the sarcin/ricin loop of rRNA. Virology. 2001;279:292-301 pubmed
    ..used to examine the relationship between depurination of the S/R loop and inhibition of +1 programmed ribosomal frameshifting (PRF) and to define PAP sequences critical for inhibition of +1 PRF and Ty1 retrotransposition in the ..
  38. Plant E, Dinman J. The role of programmed-1 ribosomal frameshifting in coronavirus propagation. Front Biosci. 2008;13:4873-81 pubmed
    ..Here we summarize current knowledge and add additional insight regarding the function of the programmed -1 ribosomal frameshift signal in the coronavirus lifecycle. ..
  39. Rosengarten R, Sperling E, Moreno M, Leys S, Dellaporta S. The mitochondrial genome of the hexactinellid sponge Aphrocallistes vastus: evidence for programmed translational frameshifting. BMC Genomics. 2008;9:33 pubmed publisher
    ..vastus has provided evidence diagnostic for +1 programmed translational frameshifting, a phenomenon disparately reported throughout the animal kingdom, but present in the hexactinellid mtDNAs that have been sequenced to date...
  40. Carlson B, Mushinski J, Henderson D, Kwon S, Crain P, Lee B, et al. 1-Methylguanosine in place of Y base at position 37 in phenylalanine tRNA is responsible for its shiftiness in retroviral ribosomal frameshifting. Virology. 2001;279:130-5 pubmed
    Many mammalian retroviruses express their protease and polymerase by ribosomal frameshifting. It was originally proposed that a specialized shifty tRNA promotes the frameshift event...
  41. Baranov P, Gurvich O, Hammer A, Gesteland R, Atkins J. RECODE 2003. Nucleic Acids Res. 2003;31:87-9 pubmed
    The RECODE database is a compilation of translational recoding events (programmed ribosomal frameshifting, codon redefinition and translational bypass)...
  42. Baril M, Dulude D, Gendron K, Lemay G, Brakier Gingras L. Efficiency of a programmed -1 ribosomal frameshift in the different subtypes of the human immunodeficiency virus type 1 group M. RNA. 2003;9:1246-53 pubmed
    ..2 kcal/mole to -26.2 kcal/mole). The fact that the frameshift efficiencies fall within a narrow range for all of the subtypes of HIV-1 group M stresses the potential of the frameshift event as an antiviral target. ..
  43. Farabaugh P, Kramer E, Vallabhaneni H, Raman A. Evolution of +1 programmed frameshifting signals and frameshift-regulating tRNAs in the order Saccharomycetales. J Mol Evol. 2006;63:545-61 pubmed
    ..The stability of the coevolution of protein coding genes and tRNAs suggests that frameshifting has been selected for during the divergence of these species. ..
  44. Plant E, Dinman J. Comparative study of the effects of heptameric slippery site composition on -1 frameshifting among different eukaryotic systems. RNA. 2006;12:666-73 pubmed
    Studies of programmed -1 ribosomal frameshifting (-1 PRF) have been approached over the past two decades by many different laboratories using a diverse array of virus-derived frameshift signals in translational assay systems derived from ..
  45. Chen C, Montelaro R. Characterization of RNA elements that regulate gag-pol ribosomal frameshifting in equine infectious anemia virus. J Virol. 2003;77:10280-7 pubmed
    ..believed that a slippery sequence and a downstream RNA structure are required for the programmed -1 ribosomal frameshifting. However, the mechanism regulating the Gag-Pol frameshifting remains poorly understood...
  46. Staple D, Venditti V, Niccolai N, Elson Schwab L, Tor Y, Butcher S. Guanidinoneomycin B recognition of an HIV-1 RNA helix. Chembiochem. 2008;9:93-102 pubmed
    ..The binding of GNB causes a broadening of the major groove across the binding site. ..
  47. Park S, Jung Y, Kim Y, Park H. Identification of novel ligands for the RNA pseudoknot that regulate -1 ribosomal frameshifting. Bioorg Med Chem. 2008;16:4676-84 pubmed publisher
    In many viruses, -1 ribosomal frameshifting (-1RF) regulates synthesis of proteins and is crucial for virus production. An RNA pseudoknot is one of the essential components of the viral -1RF system...
  48. Ivanov I, Gesteland R, Atkins J. Antizyme expression: a subversion of triplet decoding, which is remarkably conserved by evolution, is a sensor for an autoregulatory circuit. Nucleic Acids Res. 2000;28:3185-96 pubmed
    The efficiency of programmed ribosomal frameshifting in decoding antizyme mRNA is the sensor for an autoregulatory circuit that controls cellular polyamine levels in organisms ranging from the yeast Schizosaccharomyces pombe to ..
  49. Karamysheva Z, Karamyshev A, Ito K, Yokogawa T, Nishikawa K, Nakamura Y, et al. Antizyme frameshifting as a functional probe of eukaryotic translational termination. Nucleic Acids Res. 2003;31:5949-56 pubmed
    ..The system affords a convenient assay for release factor activity and has provided some novel views of the mechanism of antizyme frameshifting...
  50. Tosaka Y, Tanaka H, Yano Y, Masai K, Nozaki M, Yomogida K, et al. Identification and characterization of testis specific ornithine decarboxylase antizyme (OAZ-t) gene: expression in haploid germ cells and polyamine-induced frameshifting. Genes Cells. 2000;5:265-76 pubmed
  51. Gurvich O, Baranov P, Zhou J, Hammer A, Gesteland R, Atkins J. Sequences that direct significant levels of frameshifting are frequent in coding regions of Escherichia coli. EMBO J. 2003;22:5941-50 pubmed
    It is generally believed that significant ribosomal frameshifting during translation does not occur without a functional purpose...
  52. Palanimurugan R, Scheel H, Hofmann K, Dohmen R. Polyamines regulate their synthesis by inducing expression and blocking degradation of ODC antizyme. EMBO J. 2004;23:4857-67 pubmed
    ..The synthesis of mammalian AZ was reported to involve a polyamine-induced ribosomal frameshifting mechanism...
  53. Harger J, Meskauskas A, Dinman J. An "integrated model" of programmed ribosomal frameshifting. Trends Biochem Sci. 2002;27:448-54 pubmed