title: Asc1, homolog of human RACK1, prevents frameshifting in yeast by ribosomes stalled at CGA codon repeats.
abstract: Quality control systems monitor and stop translation at some ribosomal stalls, but it is unknown if halting translation at such stalls actually prevents synthesis of abnormal polypeptides. In yeast, ribosome stalling occurs at Arg CGA codon repeats, with even two consecutive CGA codons able to reduce translation by up to 50%. The conserved eukaryotic Asc1 protein limits translation through internal Arg CGA codon repeats. We show that, in the absence of Asc1 protein, ribosomes continue translating at CGA codons, but undergo substantial frameshifting with dramatically higher levels of frameshifting occurring with additional repeats of CGA codons. Frameshifting depends upon the slow or inefficient decoding of these codons, since frameshifting is suppressed by increased expression of the native tRNA(Arg(ICG)) that decodes CGA codons by wobble decoding. Moreover, the extent of frameshifting is modulated by the position of the CGA codon repeat relative to the translation start site. Thus, translation fidelity depends upon Asc1-mediated quality control.
authors: Department of Biochemistry and Biophysics, School of Medicine and Dentistry, University of Rochester, Rochester, New York 14642, USA.
authors: Andrew S
authors: AS
authors: Wolf
authors: Department of Biochemistry and Biophysics, School of Medicine and Dentistry, University of Rochester, Rochester, New York 14642, USA Center for RNA Biology, University of Rochester, Rochester, New York 14642, USA.
authors: Elizabeth J
authors: EJ
authors: Grayhack
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000502:physiology*; D001483:Base Sequence; D003062:Codon / Q000378:metabolism; D018388:Codon, Terminator / Q000378:metabolism; D018965:Frameshifting, Ribosomal / Q000235:genetics*; D019204:GTP-Binding Proteins / Q000235:genetics* / Q000502:physiology*; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics*; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000378:metabolism; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface / Q000235:genetics*; D012270:Ribosomes / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000502:physiology*; D017385:Sequence Homology; D024363:Transcription Initiation Site; D018911:Trinucleotide Repeats
chemical_list: C111825:ASC1 protein, S cerevisiae; D048868:Adaptor Proteins, Signal Transducing; D003062:Codon; D018388:Codon, Terminator; D009363:Neoplasm Proteins; C419368:RACK1 protein, human; D012333:RNA, Messenger; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface; D029701:Saccharomyces cerevisiae Proteins; D019204:GTP-Binding Proteins
keywords: Asc1; Rack1; frameshift; reading frame; ribosome; translation stalls