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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.

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.

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Related in: MedlinePlus

No-go mRNA decay (NGD) and protein destruction. Diverse mRNA or nascent chain features (*) that result in terminally stalled translation elongation complexes are resolved by a host of mRNA and protein destruction factors. Initial mRNA cleavage by unknown endonuclease(s) allows the alternative ribosome release factors, Hbs1 and Dom34 to mediate ribosomal splitting via Rli1 (ABCE1) and subsequent mRNA decay by RNA exonucleases. The nascent polypeptide is targeted for ubiquitylation by the Ltn1-containing ribosome quality control complex (RQC) and Not4. Hel2 and Asc1 putatively target nascent chains for ubiquitylation before and independent of the RQC.
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fig4: No-go mRNA decay (NGD) and protein destruction. Diverse mRNA or nascent chain features (*) that result in terminally stalled translation elongation complexes are resolved by a host of mRNA and protein destruction factors. Initial mRNA cleavage by unknown endonuclease(s) allows the alternative ribosome release factors, Hbs1 and Dom34 to mediate ribosomal splitting via Rli1 (ABCE1) and subsequent mRNA decay by RNA exonucleases. The nascent polypeptide is targeted for ubiquitylation by the Ltn1-containing ribosome quality control complex (RQC) and Not4. Hel2 and Asc1 putatively target nascent chains for ubiquitylation before and independent of the RQC.

Mentions: A third type of mRNA defect that activates cotranslational QC causes ribosomes to stall during translation elongation and activates the no-go decay (NGD) pathway (Fig. 4). This pathway was first discovered with the observation that insertion of a stable RNA hairpin structure that inhibits translation elongation in the S. cerevisiae PGK1 mRNA causes endonucleolytic cleavage and accelerated degradation of the mRNA (Doma and Parker, 2006). In addition to RNA structural elements, rare codons and polylysine–codon tracts (Tsuboi et al., 2012), as well as mRNA depurination by a viral enzyme (Gandhi et al., 2008), have been shown to active the NGD pathway. A possible important role of the NGD pathway is to clear the cell of mRNAs that have been subjected to chemical or irradiation-mediated RNA damage (Doma and Parker, 2006; Harigaya and Parker, 2010). Interestingly, the observation that translation of a polylysine tract within the nascent polypeptide activates the NGD pathway (Tsuboi et al., 2012) raises the question of whether a non-stop mRNA produced by premature polyadenylation within the coding region, thereby producing a polypeptide with a terminal polylysine tract, can be a target of either NGD or NSD pathways depending on whether the ribosome stalls while translating the poly(A)-tail or after reaching the mRNA 3′ end.


Protecting the proteome: Eukaryotic cotranslational quality control pathways.

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

No-go mRNA decay (NGD) and protein destruction. Diverse mRNA or nascent chain features (*) that result in terminally stalled translation elongation complexes are resolved by a host of mRNA and protein destruction factors. Initial mRNA cleavage by unknown endonuclease(s) allows the alternative ribosome release factors, Hbs1 and Dom34 to mediate ribosomal splitting via Rli1 (ABCE1) and subsequent mRNA decay by RNA exonucleases. The nascent polypeptide is targeted for ubiquitylation by the Ltn1-containing ribosome quality control complex (RQC) and Not4. Hel2 and Asc1 putatively target nascent chains for ubiquitylation before and independent of the RQC.
© Copyright Policy - openaccess
Related In: Results  -  Collection

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

fig4: No-go mRNA decay (NGD) and protein destruction. Diverse mRNA or nascent chain features (*) that result in terminally stalled translation elongation complexes are resolved by a host of mRNA and protein destruction factors. Initial mRNA cleavage by unknown endonuclease(s) allows the alternative ribosome release factors, Hbs1 and Dom34 to mediate ribosomal splitting via Rli1 (ABCE1) and subsequent mRNA decay by RNA exonucleases. The nascent polypeptide is targeted for ubiquitylation by the Ltn1-containing ribosome quality control complex (RQC) and Not4. Hel2 and Asc1 putatively target nascent chains for ubiquitylation before and independent of the RQC.
Mentions: A third type of mRNA defect that activates cotranslational QC causes ribosomes to stall during translation elongation and activates the no-go decay (NGD) pathway (Fig. 4). This pathway was first discovered with the observation that insertion of a stable RNA hairpin structure that inhibits translation elongation in the S. cerevisiae PGK1 mRNA causes endonucleolytic cleavage and accelerated degradation of the mRNA (Doma and Parker, 2006). In addition to RNA structural elements, rare codons and polylysine–codon tracts (Tsuboi et al., 2012), as well as mRNA depurination by a viral enzyme (Gandhi et al., 2008), have been shown to active the NGD pathway. A possible important role of the NGD pathway is to clear the cell of mRNAs that have been subjected to chemical or irradiation-mediated RNA damage (Doma and Parker, 2006; Harigaya and Parker, 2010). Interestingly, the observation that translation of a polylysine tract within the nascent polypeptide activates the NGD pathway (Tsuboi et al., 2012) raises the question of whether a non-stop mRNA produced by premature polyadenylation within the coding region, thereby producing a polypeptide with a terminal polylysine tract, can be a target of either NGD or NSD pathways depending on whether the ribosome stalls while translating the poly(A)-tail or after reaching the mRNA 3′ end.

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