title: Not4-dependent translational repression is important for cellular protein homeostasis in yeast.
abstract: Translation of aberrant or problematic mRNAs can cause ribosome stalling which leads to the production of truncated or defective proteins. Therefore, cells evolved cotranslational quality control mechanisms that eliminate these transcripts and target arrested nascent polypeptides for proteasomal degradation. Here we show that Not4, which is part of the multifunctional Ccr4-Not complex in yeast, associates with polysomes and contributes to the negative regulation of protein synthesis. Not4 is involved in translational repression of transcripts that cause transient ribosome stalling. The absence of Not4 affected global translational repression upon nutrient withdrawal, enhanced the expression of arrested nascent polypeptides and caused constitutive protein folding stress and aggregation. Similar defects were observed in cells with impaired mRNA decapping protein function and in cells lacking the mRNA decapping activator and translational repressor Dhh1. The results suggest a role for Not4 together with components of the decapping machinery in the regulation of protein expression on the mRNA level and emphasize the importance of translational repression for the maintenance of proteome integrity.
authors.affiliation: Molecular Microbiology, University of Konstanz, Konstanz, Germany Konstanz Research School Chemical Biology, University of Konstanz, Konstanz, Germany sp693@cam.ac.uk elke.deuerling@uni-konstanz.de.
authors.forename: Steffen
authors.initials: S
authors.lastname: Preissler
authors.affiliation: Molecular Microbiology, University of Konstanz, Konstanz, Germany Konstanz Research School Chemical Biology, University of Konstanz, Konstanz, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Reuther
authors.affiliation: Molecular Microbiology, University of Konstanz, Konstanz, Germany Konstanz Research School Chemical Biology, University of Konstanz, Konstanz, Germany.
authors.forename: Miriam
authors.initials: M
authors.lastname: Koch
authors.affiliation: Molecular Microbiology, University of Konstanz, Konstanz, Germany Konstanz Research School Chemical Biology, University of Konstanz, Konstanz, Germany.
authors.forename: Annika
authors.initials: A
authors.lastname: Scior
authors.affiliation: Molecular Microbiology, University of Konstanz, Konstanz, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Bruderek
authors.affiliation: Applied Bioinformatics, University of Konstanz, Konstanz, Germany.
authors.forename: Tancred
authors.initials: T
authors.lastname: Frickey
authors.affiliation: Molecular Microbiology, University of Konstanz, Konstanz, Germany sp693@cam.ac.uk elke.deuerling@uni-konstanz.de.
authors.forename: Elke
authors.initials: E
authors.lastname: Deuerling
mesh_terms: D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism; D004722:Endoribonucleases / Q000235:genetics / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D006706:Homeostasis; D011107:Polylysine / Q000378:metabolism; D011132:Polyribosomes / Q000235:genetics / Q000378:metabolism; D014176:Protein Biosynthesis; D039381:RNA Cap-Binding Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012097:Repressor Proteins; D012260:Ribonucleases / Q000235:genetics / Q000378:metabolism; D012270:Ribosomes / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*
chemical_list: D039381:RNA Cap-Binding Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D011107:Polylysine; C086923:MOT2 protein, S cerevisiae; D044767:Ubiquitin-Protein Ligases; C078657:CCR4 protein, S cerevisiae; C100868:DCP1 protein, S cerevisiae; D004722:Endoribonucleases; D012260:Ribonucleases; C445083:DHH1 protein, S cerevisiae; D053487:DEAD-box RNA Helicases
keywords: Ccr4–Not complex; Not4; protein homeostasis; ribosome stalling; translational repression