Abstract
Because messenger RNAs without a stop codon (nonstop mRNAs) generate stalled ribosomes, cells have developed a mechanism allowing degradation of nonstop mRNAs and their translation products (nonstop proteins) in the cytosol. Here, we observe the fate of nonstop proteins destined for organelles such as the endoplasmic reticulum (ER) and mitochondria. Nonstop mRNAs for secretory-pathway proteins in yeast generate nonstop proteins that become stuck in the translocator, the Sec61 complex, in the ER membrane. These stuck nonstop secretory proteins avoid proteasomal degradation in the cytosol, but are instead released into the ER lumen through stalled ribosome and translocator channels by Dom34:Hbs1. We also found that nonstop mitochondrial proteins are cleared from the mitochondrial translocator, the TOM40 complex, by Dom34:Hbs1. Clearance of stuck nonstop proteins from organellar translocator channels is crucial for normal protein influx into organelles and for normal cell growth, especially when nonstop mRNA decay does not function efficiently.
Copyright © 2012 The Authors. Published by Elsevier Inc. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Cell Cycle Proteins / genetics
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Cell Cycle Proteins / metabolism*
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Codon, Terminator*
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Endoplasmic Reticulum / genetics
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Endoplasmic Reticulum / metabolism*
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Endoribonucleases / genetics
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Endoribonucleases / metabolism*
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GTP-Binding Proteins / genetics
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GTP-Binding Proteins / metabolism*
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HSP70 Heat-Shock Proteins / genetics
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HSP70 Heat-Shock Proteins / metabolism*
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Intracellular Membranes / metabolism*
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Membrane Transport Proteins / genetics
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Membrane Transport Proteins / metabolism
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Mitochondria / genetics
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Mitochondria / metabolism*
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Mitochondrial Membrane Transport Proteins / genetics
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Mitochondrial Membrane Transport Proteins / metabolism
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Peptide Elongation Factors / genetics
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Peptide Elongation Factors / metabolism*
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Protein Transport / physiology
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SEC Translocation Channels
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Saccharomyces cerevisiae / genetics
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Saccharomyces cerevisiae / metabolism*
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Saccharomyces cerevisiae Proteins / genetics
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Saccharomyces cerevisiae Proteins / metabolism*
Substances
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Cell Cycle Proteins
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Codon, Terminator
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HBS1 protein, S cerevisiae
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HSP70 Heat-Shock Proteins
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Membrane Transport Proteins
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Mitochondrial Membrane Transport Proteins
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Peptide Elongation Factors
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SEC Translocation Channels
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SEC61 protein, S cerevisiae
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Saccharomyces cerevisiae Proteins
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Tom40 protein, S cerevisiae
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Dom34 protein, S cerevisiae
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Endoribonucleases
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GTP-Binding Proteins