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Protecting the proteome: Eukaryotic cotranslational quality control pathways.

Lykke-Andersen J, Bennett EJ - J. Cell Biol. (2014)

Bottom Line: The correct decoding of messenger RNAs (mRNAs) into proteins is an essential cellular task.The translational process is monitored by several quality control (QC) mechanisms that recognize defective translation complexes in which ribosomes are stalled on substrate mRNAs.These QC events promote the disassembly of the stalled translation complex and the recycling and/or degradation of the individual mRNA, ribosomal, and/or nascent polypeptide components, thereby clearing the cell of improper translation products and defective components of the translation machinery.

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Affiliation: Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093.

ABSTRACT
The correct decoding of messenger RNAs (mRNAs) into proteins is an essential cellular task. The translational process is monitored by several quality control (QC) mechanisms that recognize defective translation complexes in which ribosomes are stalled on substrate mRNAs. Stalled translation complexes occur when defects in the mRNA template, the translation machinery, or the nascent polypeptide arrest the ribosome during translation elongation or termination. These QC events promote the disassembly of the stalled translation complex and the recycling and/or degradation of the individual mRNA, ribosomal, and/or nascent polypeptide components, thereby clearing the cell of improper translation products and defective components of the translation machinery.

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Non-stop mRNA decay (NSD) and protein destruction. mRNAs on which the ribosome reaches the 3′ end without encountering a stop codon are detected by the eRF3-like factor Ski7 and targeted for mRNA decay by the exosome. The stalled ribosome is thought to be released by the Hbs1–Dom34–Rli1 complex. Extraction and destruction of the defective protein products arising from NSD mRNA substrates is mediated by ubiquitin pathway components Ltn1 and Cdc48.
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fig3: Non-stop mRNA decay (NSD) and protein destruction. mRNAs on which the ribosome reaches the 3′ end without encountering a stop codon are detected by the eRF3-like factor Ski7 and targeted for mRNA decay by the exosome. The stalled ribosome is thought to be released by the Hbs1–Dom34–Rli1 complex. Extraction and destruction of the defective protein products arising from NSD mRNA substrates is mediated by ubiquitin pathway components Ltn1 and Cdc48.

Mentions: Another type of defect that subjects mRNAs to cotranslational QC is a defect that results in the absence of a termination codon. The resulting “non-stop” mRNAs are subjected to the non-stop decay (NSD) pathway once the translating ribosome reaches the mRNA 3′ end without encountering a termination codon (Fig. 3; Frischmeyer et al., 2002; van Hoof et al., 2002). Non-stop mRNAs likely arise primarily by processing errors where polyadenylation occurs prematurely within the mRNA coding region (Frischmeyer et al., 2002; van Hoof et al., 2002). Another possible source of NSD substrates are truncated mRNAs resulting from endonucleolytic cleavage events within the protein coding region (Tsuboi et al., 2012; Matsuda et al., 2014). However, an mRNA endonucleolytically cleaved by a hammerhead ribozyme is efficiently degraded by cellular exonucleases and does not require the NSD machinery for rapid degradation, suggesting that general exonucleolytic mRNA decay pathways may dominate over the NSD pathway on such substrates (Meaux and Van Hoof, 2006).


Protecting the proteome: Eukaryotic cotranslational quality control pathways.

Lykke-Andersen J, Bennett EJ - J. Cell Biol. (2014)

Non-stop mRNA decay (NSD) and protein destruction. mRNAs on which the ribosome reaches the 3′ end without encountering a stop codon are detected by the eRF3-like factor Ski7 and targeted for mRNA decay by the exosome. The stalled ribosome is thought to be released by the Hbs1–Dom34–Rli1 complex. Extraction and destruction of the defective protein products arising from NSD mRNA substrates is mediated by ubiquitin pathway components Ltn1 and Cdc48.
© Copyright Policy - openaccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC3926952&req=5

fig3: Non-stop mRNA decay (NSD) and protein destruction. mRNAs on which the ribosome reaches the 3′ end without encountering a stop codon are detected by the eRF3-like factor Ski7 and targeted for mRNA decay by the exosome. The stalled ribosome is thought to be released by the Hbs1–Dom34–Rli1 complex. Extraction and destruction of the defective protein products arising from NSD mRNA substrates is mediated by ubiquitin pathway components Ltn1 and Cdc48.
Mentions: Another type of defect that subjects mRNAs to cotranslational QC is a defect that results in the absence of a termination codon. The resulting “non-stop” mRNAs are subjected to the non-stop decay (NSD) pathway once the translating ribosome reaches the mRNA 3′ end without encountering a termination codon (Fig. 3; Frischmeyer et al., 2002; van Hoof et al., 2002). Non-stop mRNAs likely arise primarily by processing errors where polyadenylation occurs prematurely within the mRNA coding region (Frischmeyer et al., 2002; van Hoof et al., 2002). Another possible source of NSD substrates are truncated mRNAs resulting from endonucleolytic cleavage events within the protein coding region (Tsuboi et al., 2012; Matsuda et al., 2014). However, an mRNA endonucleolytically cleaved by a hammerhead ribozyme is efficiently degraded by cellular exonucleases and does not require the NSD machinery for rapid degradation, suggesting that general exonucleolytic mRNA decay pathways may dominate over the NSD pathway on such substrates (Meaux and Van Hoof, 2006).

Bottom Line: The correct decoding of messenger RNAs (mRNAs) into proteins is an essential cellular task.The translational process is monitored by several quality control (QC) mechanisms that recognize defective translation complexes in which ribosomes are stalled on substrate mRNAs.These QC events promote the disassembly of the stalled translation complex and the recycling and/or degradation of the individual mRNA, ribosomal, and/or nascent polypeptide components, thereby clearing the cell of improper translation products and defective components of the translation machinery.

View Article: PubMed Central - HTML - PubMed

Affiliation: Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093.

ABSTRACT
The correct decoding of messenger RNAs (mRNAs) into proteins is an essential cellular task. The translational process is monitored by several quality control (QC) mechanisms that recognize defective translation complexes in which ribosomes are stalled on substrate mRNAs. Stalled translation complexes occur when defects in the mRNA template, the translation machinery, or the nascent polypeptide arrest the ribosome during translation elongation or termination. These QC events promote the disassembly of the stalled translation complex and the recycling and/or degradation of the individual mRNA, ribosomal, and/or nascent polypeptide components, thereby clearing the cell of improper translation products and defective components of the translation machinery.

Show MeSH
Related in: MedlinePlus