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PMID: 15388879 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Evidence against a direct role for the Upf proteins in frameshifting or nonsense codon readthrough.

RNA (New York, N.Y.) ·Vol. 10 ·No. 11 ·2004-11-00 ·Pages 1721-9

Harger JW, Dinman JD

Abstract

The Upf proteins are essential for nonsense-mediated mRNA decay (NMD). They have also been implicated in the modulation of translational fidelity at viral frameshift signals and premature termination codons. How these factors function in both mRNA turnover and translational control remains unclear. In this study, mono- and bicistronic reporter systems were used in the yeast Saccharomyces cerevisae to differentiate between effects at the levels of mRNA turnover and those at the level of translation. We confirm that upfDelta mutants do not affect programmed frameshifting, and show that this is also true for mutant forms of eIF1/Sui1p. Further, bicistronic reporters did not detect defects in translational readthrough due to deletion of the UPF genes, suggesting that their function in termination is not as general a phenomenon as was previously believed. The demonstration that upf sui1 double mutants are synthetically lethal demonstrates an important functional interaction between the NMD and translation initiation pathway.

MeSH Terms
Adaptor Proteins, Signal Transducing Codon, Nonsense Codon, Terminator Escherichia coli/genetics Eukaryotic Initiation Factor-1/genetics,metabolism Frameshift Mutation Fungal Proteins/genetics,metabolism Gene Deletion Genes, Fungal Genes, Reporter Lac Operon Luciferases/metabolism Peptide Initiation Factors/genetics,metabolism Protein Biosynthesis RNA Helicases/genetics,metabolism RNA Stability RNA, Messenger/metabolism RNA-Binding Proteins/genetics,metabolism Saccharomyces cerevisiae/growth & development,metabolism Saccharomyces cerevisiae Proteins/genetics,metabolism Trans-Activators/genetics,metabolism
Chemicals
Adaptor Proteins, Signal Transducing Codon, Nonsense Codon, Terminator Eukaryotic Initiation Factor-1 Fungal Proteins NMD2 protein, S cerevisiae Peptide Initiation Factors RNA, Messenger RNA-Binding Proteins SUI1 protein, S cerevisiae Saccharomyces cerevisiae Proteins Trans-Activators UPF3 protein, S cerevisiae Luciferases NAM7 protein, S cerevisiae RNA Helicases
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Harger Jason W
Department of Cell Biology and Molecular Genetics, 2135 Microbiology Building, University of Maryland, College Park, MD 20742, USA.
Dinman Jonathan D
References (59)
59 references, click to expand
  1. An internal open reading frame triggers nonsense-mediated decay of the yeast SPT10 mRNA.
    EMBO J. 1999 Nov 1;18(21):6134-45 PMID: 10545123
  2. Association of the yeast poly(A) tail binding protein with translation initiation factor eIF-4G.
    EMBO J. 1996 Dec 16;15(24):7168-77 PMID: 9003792
  3. Upf1p control of nonsense mRNA translation is regulated by Nmd2p and Upf3p.
    Mol Cell Biol. 2000 Jul;20(13):4591-603 PMID: 10848586
  4. The yeast hnRNP-like protein Hrp1/Nab4 marks a transcript for nonsense-mediated mRNA decay.
    Mol Cell. 2000 Mar;5(3):489-99 PMID: 10882134
  5. The RNA binding protein Pub1 modulates the stability of transcripts containing upstream open reading frames.
    Cell. 2000 Jun 23;101(7):741-51 PMID: 10892745
  6. Nonsense-mediated decay mutants do not affect programmed -1 frameshifting.
    RNA. 2000 Jul;6(7):952-61 PMID: 10917592
  7. Novel Upf2p orthologues suggest a functional link between translation initiation and nonsense surveillance complexes.
    Mol Cell Biol. 2000 Dec;20(23):8944-57 PMID: 11073994
  8. The case for the involvement of the Upf3p in programmed -1 ribosomal frameshifting.
    RNA. 2000 Dec;6(12):1685-6 PMID: 11142366
  9. The case against the involvement of the NMD proteins in programmed frameshifting.
    RNA. 2000 Dec;6(12):1687-8 PMID: 11142367
  10. The role of Upf proteins in modulating the translation read-through of nonsense-containing transcripts.
    EMBO J. 2001 Feb 15;20(4):880-90 PMID: 11179232
  11. Quality control of mRNA function.
    Cell. 2001 Jan 26;104(2):173-6 PMID: 11207359
  12. A subcomplex of three eIF3 subunits binds eIF1 and eIF5 and stimulates ribosome binding of mRNA and tRNA(i)Met.
    EMBO J. 2001 Jun 1;20(11):2954-65 PMID: 11387228
  13. Absence of Dbp2p alters both nonsense-mediated mRNA decay and rRNA processing.
    Mol Cell Biol. 2001 Nov;21(21):7366-79 PMID: 11585918
  14. Nonsense-mediated mRNA decay in Saccharomyces cerevisiae.
    Gene. 2001 Aug 22;274(1-2):15-25 PMID: 11674994
  15. Curbing the nonsense: the activation and regulation of mRNA surveillance.
    Genes Dev. 2001 Nov 1;15(21):2781-5 PMID: 11691829
  16. mRNA surveillance: the perfect persist.
    J Cell Sci. 2002 Aug 1;115(Pt 15):3033-8 PMID: 12118059
  17. An "integrated model" of programmed ribosomal frameshifting.
    Trends Biochem Sci. 2002 Sep;27(9):448-54 PMID: 12217519
  18. The roles of individual eukaryotic translation initiation factors in ribosomal scanning and initiation codon selection.
    Genes Dev. 2002 Nov 15;16(22):2906-22 PMID: 12435632
  19. An NMD pathway in yeast involving accelerated deadenylation and exosome-mediated 3'-->5' degradation.
    Mol Cell. 2003 May;11(5):1405-13 PMID: 12769863
  20. An in vivo dual-luciferase assay system for studying translational recoding in the yeast Saccharomyces cerevisiae.
    RNA. 2003 Aug;9(8):1019-24 PMID: 12869712
  21. Interaction between Ski7p and Upf1p is required for nonsense-mediated 3'-to-5' mRNA decay in yeast.
    EMBO J. 2003 Aug 1;22(15):3951-9 PMID: 12881429
  22. Genome-wide analysis of mRNAs regulated by the nonsense-mediated and 5' to 3' mRNA decay pathways in yeast.
    Mol Cell. 2003 Dec;12(6):1439-52 PMID: 14690598
  23. Leaky termination at premature stop codons antagonizes nonsense-mediated mRNA decay in S. cerevisiae.
    RNA. 2004 Apr;10(4):691-703 PMID: 15037778
  24. Two chromosomal genes required for killing expression in killer strains of Saccharomyces cerevisiae.
    Genetics. 1976 Mar 25;82(3):429-42 PMID: 773743
  25. Frameshift suppression Saccharomyces cerevisiae. II. Genetic properties of group II suppressors.
    Genetics. 1980 Aug;95(4):833-53 PMID: 7009318
  26. Yeast ochre suppressor SUQ5-ol is an altered tRNA Ser UCA.
    Nucleic Acids Res. 1981 Jul 10;9(13):3077-88 PMID: 7024909
  27. Transformation of intact yeast cells treated with alkali cations.
    J Bacteriol. 1983 Jan;153(1):163-8 PMID: 6336730
  28. Eukaryotic ribosomes require initiation factors 1 and 1A to locate initiation codons.
    Nature. 1998 Aug 27;394(6696):854-9 PMID: 9732867
  29. A newly identified N-terminal amino acid sequence of human eIF4G binds poly(A)-binding protein and functions in poly(A)-dependent translation.
    EMBO J. 1998 Dec 15;17(24):7480-9 PMID: 9857202
  30. The Mof2/Sui1 protein is a general monitor of translational accuracy.
    Mol Cell Biol. 1998 Mar;18(3):1506-16 PMID: 9488467
  31. ATP is a cofactor of the Upf1 protein that modulates its translation termination and RNA binding activities.
    RNA. 1998 Feb;4(2):205-14 PMID: 9570320
  32. The surveillance complex interacts with the translation release factors to enhance termination and degrade aberrant mRNAs.
    Genes Dev. 1998 Jun 1;12(11):1665-77 PMID: 9620853
  33. A dual-luciferase reporter system for studying recoding signals.
    RNA. 1998 Apr;4(4):479-86 PMID: 9630253
  34. The upf3 protein is a component of the surveillance complex that monitors both translation and mRNA turnover and affects viral propagation.
    Proc Natl Acad Sci U S A. 1998 Jul 21;95(15):8721-6 PMID: 9671745
  35. A perfect message: RNA surveillance and nonsense-mediated decay.
    Cell. 1999 Feb 5;96(3):307-10 PMID: 10025395
  36. The yeast poly(A)-binding protein Pab1p stimulates in vitro poly(A)-dependent and cap-dependent translation by distinct mechanisms.
    EMBO J. 1999 Jun 1;18(11):3153-63 PMID: 10357826
  37. mRNA surveillance in eukaryotes: kinetic proofreading of proper translation termination as assessed by mRNP domain organization?
    RNA. 1999 Jun;5(6):711-9 PMID: 10376871
  38. Mutations in the MOF2/SUI1 gene affect both translation and nonsense-mediated mRNA decay.
    RNA. 1999 Jun;5(6):794-804 PMID: 10376878
  39. Yeast Upf proteins required for RNA surveillance affect global expression of the yeast transcriptome.
    Mol Cell Biol. 1999 Oct;19(10):6710-9 PMID: 10490610
  40. The DCP2 protein is required for mRNA decapping in Saccharomyces cerevisiae and contains a functional MutT motif.
    EMBO J. 1999 Oct 1;18(19):5411-22 PMID: 10508173
  41. Identifying the right stop: determining how the surveillance complex recognizes and degrades an aberrant mRNA.
    EMBO J. 1998 Jan 15;17(2):575-89 PMID: 9430648
  42. Genetic selection for mutations that reduce or abolish ribosomal recognition of the HIS4 translational initiator region.
    Mol Cell Biol. 1988 Jul;8(7):2955-63 PMID: 3043200
  43. The product of the yeast UPF1 gene is required for rapid turnover of mRNAs containing a premature translational termination codon.
    Genes Dev. 1991 Dec;5(12A):2303-14 PMID: 1748286
  44. The suil suppressor locus in Saccharomyces cerevisiae encodes a translation factor that functions during tRNA(iMet) recognition of the start codon.
    Mol Cell Biol. 1992 Jan;12(1):248-60 PMID: 1729602
  45. Gene products that promote mRNA turnover in Saccharomyces cerevisiae.
    Mol Cell Biol. 1992 May;12(5):2165-77 PMID: 1569946
  46. 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
  47. Translational maintenance of frame: mutants of Saccharomyces cerevisiae with altered -1 ribosomal frameshifting efficiencies.
    Genetics. 1994 Jan;136(1):75-86 PMID: 8138178
  48. Premature translational termination triggers mRNA decapping.
    Nature. 1994 Aug 18;370(6490):578-81 PMID: 8052314
  49. Identification and characterization of genes that are required for the accelerated degradation of mRNAs containing a premature translational termination codon.
    Genes Dev. 1995 Feb 15;9(4):423-36 PMID: 7883167
  50. Identification of a novel component of the nonsense-mediated mRNA decay pathway by use of an interacting protein screen.
    Genes Dev. 1995 Feb 15;9(4):437-54 PMID: 7883168
  51. Decoying the cap- mRNA degradation system by a double-stranded RNA virus and poly(A)- mRNA surveillance by a yeast antiviral system.
    Mol Cell Biol. 1995 May;15(5):2763-71 PMID: 7739557
  52. The efficiency of translation termination is determined by a synergistic interplay between upstream and downstream sequences in Saccharomyces cerevisiae.
    J Mol Biol. 1995 Aug 18;251(3):334-45 PMID: 7650736
  53. Identification of an additional gene required for eukaryotic nonsense mRNA turnover.
    Proc Natl Acad Sci U S A. 1995 Oct 24;92(22):10354-8 PMID: 7479783
  54. Ribosomal frameshifting in yeast viruses.
    Yeast. 1995 Sep 30;11(12):1115-27 PMID: 8619310
  55. Genetic and biochemical characterization of mutations in the ATPase and helicase regions of the Upf1 protein.
    Mol Cell Biol. 1996 Oct;16(10):5477-90 PMID: 8816461
  56. Identification and characterization of mutations in the UPF1 gene that affect nonsense suppression and the formation of the Upf protein complex but not mRNA turnover.
    Mol Cell Biol. 1996 Oct;16(10):5491-506 PMID: 8816462
  57. Mof4-1 is an allele of the UPF1/IFS2 gene which affects both mRNA turnover and -1 ribosomal frameshifting efficiency.
    EMBO J. 1996 Oct 15;15(20):5726-36 PMID: 8896465
  58. Prions and RNA viruses of Saccharomyces cerevisiae.
    Annu Rev Genet. 1996;30:109-39 PMID: 8982451
  59. Recognition of yeast mRNAs as "nonsense containing" leads to both inhibition of mRNA translation and mRNA degradation: implications for the control of mRNA decapping.
    Mol Biol Cell. 1999 Nov;10(11):3971-8 PMID: 10564284
Article Info
Journal
RNA (New York, N.Y.)
Abbr.
RNA
ISSN
1355-8382
DOI
10.1261/rna.7120504
Published
2004-11-00
Epub
2004-00-23
Pages
1721-9
Language
English
Region
United States
NLM ID
9509184
PMCID
PMC1236997
Subset
IM
Grants
NIGMS NIH HHS · R01 GM058859 · United States
NIGMS NIH HHS · R01 GM062143 · United States
NIGMS NIH HHS · GM58859 · United States
NIGMS NIH HHS · GM62143 · United States
External Links
PubMed source DOI: 10.1261/rna.7120504 PMC Full Text View journal details
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