title: Asc1, Hel2, and Slh1 couple translation arrest to nascent chain degradation.
abstract: Premature arrest of protein synthesis within the open reading frame elicits a protective response that degrades the incomplete nascent chain. In this response, arrested 80S ribosomes are split into their large and small subunits, allowing assembly of the ribosome quality control complex (RQC), which targets nascent chains for degradation. How the cell recognizes arrested nascent chains among the vast pool of actively translating polypeptides is poorly understood. We systematically examined translation arrest and modification of nascent chains inSaccharomyces cerevisiaeto characterize the steps that couple arrest to RQC targeting. We focused our analysis on two poorly understood 80S ribosome-binding proteins previously implicated in the response to failed translation, Asc1 and Hel2, as well as a new component of the pathway, Slh1, that we identified here. We found that premature arrest at ribosome stalling sequences still occurred robustly in the absence of Asc1, Hel2, and Slh1. However, these three factors were required for the RQC to modify the nascent chain. We propose that Asc1, Hel2, and Slh1 target arresting ribosomes and that this targeting event is a precondition for the RQC to engage the incomplete nascent chain and facilitate its degradation.
authors.affiliation: Department of Biochemistry, Stanford University, Stanford, California 94305, USA.
authors.forename: Cole S
authors.initials: CS
authors.lastname: Sitron
authors.affiliation: Department of Biochemistry, Stanford University, Stanford, California 94305, USA.
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Park
authors.affiliation: Department of Biochemistry, Stanford University, Stanford, California 94305, USA.
authors.forename: Onn
authors.initials: O
authors.lastname: Brandman
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism / Q000502:physiology*; D053487:DEAD-box RNA Helicases / Q000378:metabolism / Q000502:physiology*; D019204:GTP-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D012270:Ribosomes / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism / Q000502:physiology*; D059467:Transcriptome; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism / Q000502:physiology*
chemical_list: C111825:ASC1 protein, S cerevisiae; D048868:Adaptor Proteins, Signal Transducing; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D029701:Saccharomyces cerevisiae Proteins; C577605:Hel2 protein, S cerevisiae; D044767:Ubiquitin-Protein Ligases; D019204:GTP-Binding Proteins; C432685:SLH1 protein, S cerevisiae; D053487:DEAD-box RNA Helicases
keywords: Asc1, Hel2, Slh1, Ltn1, Rqc2, Ykr023w, Cue3; CAT tails; protein quality control; ribosome stalling; translation