Protein quality control systems associated with <scp>n</scp>o‐<scp>g</scp>o and <scp>n</scp>onstop m<scp>RNA</scp> surveillance in yeast

Matsuda, Ryotaro; Ikeuchi, Ken; Nomura, Sene; Inada, Toshifumi

doi:10.1111/gtc.12106

Cited by 54 publications

(61 citation statements)

References 33 publications

(157 reference statements)

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“…Thus, Ltn1 was involved not only in the efficient degradation of nascent proteins containing polylysine segments but also in the degradation of stop codon-less proteins. A similar observation was recently reported for a different stop codon-less reporter protein (65). In contrast to Ltn1, the role of RAC/Ssb was confined to the expression of the polylysine reporter.…”

Section: Resultssupporting

confidence: 86%

Release Factor eRF3 Mediates Premature Translation Termination on Polylysine-Stalled Ribosomes in Saccharomyces cerevisiae

Chiabudini

Tais

Zhang

et al. 2014

Molecular and Cellular Biology

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bRibosome stalling is an important incident enabling the cellular quality control machinery to detect aberrant mRNA. Saccharomyces cerevisiae Hbs1-Dom34 and Ski7 are homologs of the canonical release factor eRF3-eRF1, which recognize stalled ribosomes, promote ribosome release, and induce the decay of aberrant mRNA. Polyadenylated nonstop mRNA encodes aberrant proteins containing C-terminal polylysine segments which cause ribosome stalling due to electrostatic interaction with the ribosomal exit tunnel. Here we describe a novel mechanism, termed premature translation termination, which releases C-terminally truncated translation products from ribosomes stalled on polylysine segments. Premature termination during polylysine synthesis was abolished when ribosome stalling was prevented due to the absence of the ribosomal protein Asc1. In contrast, premature termination was enhanced, when the general rate of translation elongation was lowered. The unconventional termination event was independent of Hbs1-Dom34 and Ski7, but it was dependent on eRF3. Moreover, premature termination during polylysine synthesis was strongly increased in the absence of the ribosome-bound chaperones ribosome-associated complex (RAC) and Ssb (Ssb1 and Ssb2). On the basis of the data, we suggest a model in which eRF3-eRF1 can catalyze the release of nascent polypeptides even though the ribosomal A-site contains a sense codon when the rate of translation is abnormally low.

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Section: Resultssupporting

confidence: 86%

Release Factor eRF3 Mediates Premature Translation Termination on Polylysine-Stalled Ribosomes in Saccharomyces cerevisiae

Chiabudini

Tais

Zhang

et al. 2014

Molecular and Cellular Biology

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“…This suggests that E3s other than Rkr1 contribute to ERAD-RA. One candidate E3 is Not4, which has been implicated in the degradation of a subset of cytosolic ribosome-associated degradation substrates (11,65). Ubr1 has also been shown to co-translationally target for degradation proteins with N-terminal degrons (66).…”

Section: Discussionmentioning

confidence: 99%

Rkr1/Ltn1 Ubiquitin Ligase-mediated Degradation of Translationally Stalled Endoplasmic Reticulum Proteins

Crowder

Geigges

Gibson

et al. 2015

Journal of Biological Chemistry

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Background: Translationally stalled proteins (including those aberrantly translated beyond their stop codons) pose dangers for eukaryotic cells. Results: The ubiquitin ligase Rkr1/Ltn1 targets translationally stalled ER-associated proteins for degradation. Conclusion: Cytosolic and ER-associated translationally stalled proteins are targeted for destruction by related mechanisms. Significance: Mechanisms regulating the degradation of translationally stalled ER-associated proteins may represent therapeutic targets for human disease.

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“…To test this model, we analyzed a verified RQC substrate, GFP-Rz, that arrests without the need of trans-acting factors and is split by a Dom34-dependent pathway (Tsuboi et al 2012;Matsuda et al 2014). GFP-Rz contains a hammerhead ribozyme sequence that causes self-cleavage of the mRNA (Düvel et al 2002) after the GFP sequence, resulting in a stop codon-less transcript.…”

Section: Slh1 Is a Novel Component Of The Rqc Pathway That Acts Upstrmentioning

confidence: 99%

Asc1, Hel2, and Slh1 couple translation arrest to nascent chain degradation

Sitron

Park

Brandman

2017

RNA

124

150

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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 in Saccharomyces cerevisiae to 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.

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Protein quality control systems associated with no‐go and nonstop mRNA surveillance in yeast

Cited by 54 publications

References 33 publications

Release Factor eRF3 Mediates Premature Translation Termination on Polylysine-Stalled Ribosomes in Saccharomyces cerevisiae

Release Factor eRF3 Mediates Premature Translation Termination on Polylysine-Stalled Ribosomes in Saccharomyces cerevisiae

Rkr1/Ltn1 Ubiquitin Ligase-mediated Degradation of Translationally Stalled Endoplasmic Reticulum Proteins

Asc1, Hel2, and Slh1 couple translation arrest to nascent chain degradation

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