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PMID: 12554858 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S. Review

The 9-A solution: how mRNA pseudoknots promote efficient programmed -1 ribosomal frameshifting.

RNA (New York, N.Y.) ·Vol. 9 ·No. 2 ·2003-02-00 ·Pages 168-74

Plant EP, Jacobs KL, Harger JW, Meskauskas A, Jacobs JL, Baxter JL, Petrov AN, Dinman JD

Abstract

There is something special about mRNA pseudoknots that allows them to elicit efficient levels of programmed -1 ribosomal frameshifting. Here, we present a synthesis of recent crystallographic, molecular, biochemical, and genetic studies to explain this property. Movement of 9 A by the anticodon loop of the aminoacyl-tRNA at the accommodation step normally pulls the downstream mRNA a similar distance along with it. We suggest that the downstream mRNA pseudoknot provides resistance to this movement by becoming wedged into the entrance of the ribosomal mRNA tunnel. These two opposing forces result in the creation of a local region of tension in the mRNA between the A-site codon and the mRNA pseudoknot. This can be relieved by one of two mechanisms; unwinding the pseudoknot, allowing the downstream region to move forward, or by slippage of the proximal region of the mRNA backwards by one base. The observed result of the latter mechanism is a net shift of reading frame by one base in the 5' direction, that is, a -1 ribosomal frameshift.

MeSH Terms
Bacteria/chemistry,metabolism Frameshifting, Ribosomal/physiology RNA, Messenger/chemistry,metabolism Ribosomes/metabolism Thermodynamics
Chemicals
RNA, Messenger
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Plant Ewan P
Department of Cell Biology and Molecular Genetics, Microbiology Building, University of Maryland, College Park, MD 20742, USA.
Jacobs Kristi L Muldoon
Harger Jason W
Meskauskas Arturas
Jacobs Jonathan L
Baxter Jennifer L
Petrov Alexey N
Dinman Jonathan D
References (60)
60 references, click to expand
  1. Recognition of cognate transfer RNA by the 30S ribosomal subunit.
    Science. 2001 May 4;292(5518):897-902 PMID: 11340196
  2. Ribosomal movement impeded at a pseudoknot required for frameshifting.
    Proc Natl Acad Sci U S A. 1992 Sep 15;89(18):8636-40 PMID: 1528874
  3. Visualization of tRNA movements on the Escherichia coli 70S ribosome during the elongation cycle.
    J Cell Biol. 2000 Aug 7;150(3):447-60 PMID: 10931859
  4. The complete atomic structure of the large ribosomal subunit at 2.4 A resolution.
    Science. 2000 Aug 11;289(5481):905-20 PMID: 10937989
  5. The structural basis of ribosome activity in peptide bond synthesis.
    Science. 2000 Aug 11;289(5481):920-30 PMID: 10937990
  6. Structure of functionally activated small ribosomal subunit at 3.3 angstroms resolution.
    Cell. 2000 Sep 1;102(5):615-23 PMID: 11007480
  7. Structure of the 30S ribosomal subunit.
    Nature. 2000 Sep 21;407(6802):327-39 PMID: 11014182
  8. Functional insights from the structure of the 30S ribosomal subunit and its interactions with antibiotics.
    Nature. 2000 Sep 21;407(6802):340-8 PMID: 11014183
  9. 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 Jan 5;279(1):292-301 PMID: 11145910
  10. Crystal structures of complexes of the small ribosomal subunit with tetracycline, edeine and IF3.
    EMBO J. 2001 Apr 17;20(8):1829-39 PMID: 11296217
  11. RNA tertiary interactions in the large ribosomal subunit: the A-minor motif.
    Proc Natl Acad Sci U S A. 2001 Apr 24;98(9):4899-903 PMID: 11296253
  12. Crystal structure of the ribosome at 5.5 A resolution.
    Science. 2001 May 4;292(5518):883-96 PMID: 11283358
  13. Ty1 retrotransposition and programmed +1 ribosomal frameshifting require the integrity of the protein synthetic translocation step.
    Virology. 2001 Jul 20;286(1):216-24 PMID: 11448174
  14. Analysis of mutations at residues A2451 and G2447 of 23S rRNA in the peptidyltransferase active site of the 50S ribosomal subunit.
    Proc Natl Acad Sci U S A. 2001 Jul 31;98(16):9002-7 PMID: 11470897
  15. The path of messenger RNA through the ribosome.
    Cell. 2001 Jul 27;106(2):233-41 PMID: 11511350
  16. Architecture of the protein-conducting channel associated with the translating 80S ribosome.
    Cell. 2001 Nov 2;107(3):361-72 PMID: 11701126
  17. Structure of the 80S ribosome from Saccharomyces cerevisiae--tRNA-ribosome and subunit-subunit interactions.
    Cell. 2001 Nov 2;107(3):373-86 PMID: 11701127
  18. Ribosomal pausing at a frameshifter RNA pseudoknot is sensitive to reading phase but shows little correlation with frameshift efficiency.
    Mol Cell Biol. 2001 Dec;21(24):8657-70 PMID: 11713298
  19. High resolution structure of the large ribosomal subunit from a mesophilic eubacterium.
    Cell. 2001 Nov 30;107(5):679-88 PMID: 11733066
  20. Influence of the stacking potential of the base 3' of tandem shift codons on -1 ribosomal frameshifting used for gene expression.
    RNA. 2002 Jan;8(1):16-28 PMID: 11871658
  21. A pre-translocational intermediate in protein synthesis observed in crystals of enzymatically active 50S subunits.
    Nat Struct Biol. 2002 Mar;9(3):225-30 PMID: 11828326
  22. Translocation of tRNA during protein synthesis.
    FEBS Lett. 2002 Mar 6;514(1):11-6 PMID: 11904173
  23. The transorientation hypothesis for codon recognition during protein synthesis.
    Nature. 2002 Mar 21;416(6878):281-5 PMID: 11907568
  24. Metal ions and flexibility in a viral RNA pseudoknot at atomic resolution.
    Proc Natl Acad Sci U S A. 2002 Apr 2;99(7):4302-7 PMID: 11904368
  25. Ribosome structure: revisiting the connection between translational accuracy and unconventional decoding.
    Trends Biochem Sci. 2002 Apr;27(4):178-83 PMID: 11943544
  26. The frameshift signal of HIV-1 involves a potential intramolecular triplex RNA structure.
    Proc Natl Acad Sci U S A. 2002 Apr 16;99(8):5331-6 PMID: 11959986
  27. Accurate translocation of mRNA by the ribosome requires a peptidyl group or its analog on the tRNA moving into the 30S P site.
    Mol Cell. 2002 May;9(5):1125-31 PMID: 12049747
  28. 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 Aug 20;99(17):11133-8 PMID: 12149516
  29. Mutational analysis of the "slippery-sequence" component of a coronavirus ribosomal frameshifting signal.
    J Mol Biol. 1992 Sep 20;227(2):463-79 PMID: 1404364
  30. Ribosomal pausing during translation of an RNA pseudoknot.
    Mol Cell Biol. 1993 Nov;13(11):6931-40 PMID: 8413285
  31. Translational maintenance of frame: mutants of Saccharomyces cerevisiae with altered -1 ribosomal frameshifting efficiencies.
    Genetics. 1994 Jan;136(1):75-86 PMID: 8138178
  32. The sequences of and distance between two cis-acting signals determine the efficiency of ribosomal frameshifting in human immunodeficiency virus type 1 and human T-cell leukemia virus type II in vivo.
    J Virol. 1994 Sep;68(9):6087-91 PMID: 8057488
  33. Ribosomal frameshifting viral RNAs.
    J Gen Virol. 1995 Aug;76 ( Pt 8):1885-92 PMID: 7636469
  34. Ribosomal frameshifting in yeast viruses.
    Yeast. 1995 Sep 30;11(12):1115-27 PMID: 8619310
  35. Recoding: dynamic reprogramming of translation.
    Annu Rev Biochem. 1996;65:741-68 PMID: 8811194
  36. Programmed translational frameshifting.
    Microbiol Rev. 1996 Mar;60(1):103-34 PMID: 8852897
  37. 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 Jun 24;94(13):6606-11 PMID: 9192612
  38. The pokeweed antiviral protein specifically inhibits Ty1-directed +1 ribosomal frameshifting and retrotransposition in Saccharomyces cerevisiae.
    J Virol. 1998 Feb;72(2):1036-42 PMID: 9444997
  39. Eukaryotic ribosomes require initiation factors 1 and 1A to locate initiation codons.
    Nature. 1998 Aug 27;394(6696):854-9 PMID: 9732867
  40. Primer extension analysis of eukaryotic ribosome-mRNA complexes.
    Nucleic Acids Res. 1998 Nov 1;26(21):4853-9 PMID: 9776744
  41. Minor groove RNA triplex in the crystal structure of a ribosomal frameshifting viral pseudoknot.
    Nat Struct Biol. 1999 Mar;6(3):285-92 PMID: 10074948
  42. The role of RNA pseudoknot stem 1 length in the promotion of efficient -1 ribosomal frameshifting.
    J Mol Biol. 1999 May 7;288(3):305-20 PMID: 10329144
  43. Major rearrangements in the 70S ribosomal 3D structure caused by a conformational switch in 16S ribosomal RNA.
    EMBO J. 1999 Nov 15;18(22):6501-7 PMID: 10562562
  44. Specific mutations in a viral RNA pseudoknot drastically change ribosomal frameshifting efficiency.
    Proc Natl Acad Sci U S A. 1999 Dec 7;96(25):14234-9 PMID: 10588689
  45. A highly conserved mechanism of regulated ribosome stalling mediated by fungal arginine attenuator peptides that appears independent of the charging status of arginyl-tRNAs.
    J Biol Chem. 1999 Dec 31;274(53):37565-74 PMID: 10608810
  46. Kinetics of ribosomal pausing during programmed -1 translational frameshifting.
    Mol Cell Biol. 2000 Feb;20(4):1095-103 PMID: 10648594
  47. The 3D arrangement of the 23 S and 5 S rRNA in the Escherichia coli 50 S ribosomal subunit based on a cryo-electron microscopic reconstruction at 7.5 A resolution.
    J Mol Biol. 2000 Apr 21;298(1):35-59 PMID: 10756104
  48. Structure, stability and function of RNA pseudoknots involved in stimulating ribosomal frameshifting.
    J Mol Biol. 2000 Apr 28;298(2):167-85 PMID: 10764589
  49. Single-molecule studies of DNA mechanics.
    Curr Opin Struct Biol. 2000 Jun;10(3):279-85 PMID: 10851197
  50. A ratchet-like inter-subunit reorganization of the ribosome during translocation.
    Nature. 2000 Jul 20;406(6793):318-22 PMID: 10917535
  51. 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 Aug;8(8):981-96 PMID: 12212853
  52. An "integrated model" of programmed ribosomal frameshifting.
    Trends Biochem Sci. 2002 Sep;27(9):448-54 PMID: 12217519
  53. Solution structure of a luteoviral P1-P2 frameshifting mRNA pseudoknot.
    J Mol Biol. 2002 Sep 20;322(3):621-33 PMID: 12225754
  54. The gag and pol genes of bovine leukemia virus: nucleotide sequence and analysis.
    Virology. 1985 Apr 30;142(2):357-77 PMID: 2997990
  55. Intermediate states in the movement of transfer RNA in the ribosome.
    Nature. 1989 Nov 9;342(6246):142-8 PMID: 2682263
  56. Translational suppression in gene expression in retroviruses and retrotransposons.
    Curr Top Microbiol Immunol. 1990;157:93-124 PMID: 2168307
  57. E. coli ribosomes re-phase on retroviral frameshift signals at rates ranging from 2 to 50 percent.
    New Biol. 1989 Nov;1(2):159-69 PMID: 2562219
  58. Identification and analysis of the gag-pol ribosomal frameshift site of feline immunodeficiency virus.
    Virology. 1992 Feb;186(2):389-97 PMID: 1310175
  59. Ribosomal frameshifting efficiency and gag/gag-pol ratio are critical for yeast M1 double-stranded RNA virus propagation.
    J Virol. 1992 Jun;66(6):3669-76 PMID: 1583726
  60. Ribosomal peptidyl transferase can withstand mutations at the putative catalytic nucleotide.
    Nature. 2001 May 24;411(6836):498-501 PMID: 11373685
Article Info
Journal
RNA (New York, N.Y.)
Abbr.
RNA
ISSN
1355-8382
Published
2003-02-00
Pages
168-74
Language
English
Region
United States
NLM ID
9509184
PMCID
PMC1237042
Subset
IM
Grants
NIGMS NIH HHS · R01 GM058859 · United States
NIAID NIH HHS · T32 AI051967 · United States
NIGMS NIH HHS · GM 58859 · United States
NIAID NIH HHS · T32 AI 51967 · United States
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