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CAT-tailing as a fail-safe mechanism for efficient degradation of stalled nascent polypeptides.

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Title: CAT-tailing as a fail-safe mechanism for efficient degradation of stalled nascent polypeptides.
Authors: Kostova, Kamena K., Hickey, Kelsey L., Osuna, Beatriz A., Hussmann, Jeffrey A., Frost, Adam, Weinberg, David E., Weissman, Jonathan S.
Source: Science (pre-March 2025). 7/28/2017, Vol. 357 Issue 6349, p414-417. 4p. 4 Diagrams.
Subjects: Ribosomes, Polypeptides, Alanine, Budding (Plant propagation), Lysine
Abstract: Ribosome stalling leads to recruitment of the ribosome quality control complex (RQC), which targets the partially synthesized polypeptide for proteasomal degradation through the action of the ubiquitin ligase Ltn1p. A second core RQC component, Rqc2p, modifies the nascent polypeptide by adding a carboxyl-terminal alanine and threonine (CAT) tail through a noncanonical elongation reaction. Here we examined the role of CAT-tailing in nascent-chain degradation in budding yeast. We found that Ltn1p efficiently accessed only nascent-chain lysines immediately proximal to the ribosome exit tunnel. For substrates without Ltn1p-accessible lysines, CAT-tailing enabled degradation by exposing lysines sequestered in the ribosome exit tunnel. Thus, CAT-tails do not serve as a degron, but rather provide a fail-safe mechanism that expands the range of RQC-degradable substrates. [ABSTRACT FROM AUTHOR]
Copyright of Science (pre-March 2025) is the property of American Association for the Advancement of Science and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Psychology and Behavioral Sciences Collection
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  Data: CAT-tailing as a fail-safe mechanism for efficient degradation of stalled nascent polypeptides.
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  Data: <searchLink fieldCode="AR" term="%22Kostova%2C+Kamena+K%2E%22">Kostova, Kamena K.</searchLink><br /><searchLink fieldCode="AR" term="%22Hickey%2C+Kelsey+L%2E%22">Hickey, Kelsey L.</searchLink><br /><searchLink fieldCode="AR" term="%22Osuna%2C+Beatriz+A%2E%22">Osuna, Beatriz A.</searchLink><br /><searchLink fieldCode="AR" term="%22Hussmann%2C+Jeffrey+A%2E%22">Hussmann, Jeffrey A.</searchLink><br /><searchLink fieldCode="AR" term="%22Frost%2C+Adam%22">Frost, Adam</searchLink><br /><searchLink fieldCode="AR" term="%22Weinberg%2C+David+E%2E%22">Weinberg, David E.</searchLink><br /><searchLink fieldCode="AR" term="%22Weissman%2C+Jonathan+S%2E%22">Weissman, Jonathan S.</searchLink>
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  Data: <searchLink fieldCode="JN" term="%22Science+%28pre-March+2025%29%22">Science (pre-March 2025)</searchLink>. 7/28/2017, Vol. 357 Issue 6349, p414-417. 4p. 4 Diagrams.
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  Data: <searchLink fieldCode="DE" term="%22Ribosomes%22">Ribosomes</searchLink><br /><searchLink fieldCode="DE" term="%22Polypeptides%22">Polypeptides</searchLink><br /><searchLink fieldCode="DE" term="%22Alanine%22">Alanine</searchLink><br /><searchLink fieldCode="DE" term="%22Budding+%28Plant+propagation%29%22">Budding (Plant propagation)</searchLink><br /><searchLink fieldCode="DE" term="%22Lysine%22">Lysine</searchLink>
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  Label: Abstract
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  Data: Ribosome stalling leads to recruitment of the ribosome quality control complex (RQC), which targets the partially synthesized polypeptide for proteasomal degradation through the action of the ubiquitin ligase Ltn1p. A second core RQC component, Rqc2p, modifies the nascent polypeptide by adding a carboxyl-terminal alanine and threonine (CAT) tail through a noncanonical elongation reaction. Here we examined the role of CAT-tailing in nascent-chain degradation in budding yeast. We found that Ltn1p efficiently accessed only nascent-chain lysines immediately proximal to the ribosome exit tunnel. For substrates without Ltn1p-accessible lysines, CAT-tailing enabled degradation by exposing lysines sequestered in the ribosome exit tunnel. Thus, CAT-tails do not serve as a degron, but rather provide a fail-safe mechanism that expands the range of RQC-degradable substrates. [ABSTRACT FROM AUTHOR]
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  Data: <i>Copyright of Science (pre-March 2025) is the property of American Association for the Advancement of Science and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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      – Type: doi
        Value: 10.1126/science.aam7787
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      – Code: eng
        Text: English
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        PageCount: 4
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    Subjects:
      – SubjectFull: Ribosomes
        Type: general
      – SubjectFull: Polypeptides
        Type: general
      – SubjectFull: Alanine
        Type: general
      – SubjectFull: Budding (Plant propagation)
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      – SubjectFull: Lysine
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      – TitleFull: CAT-tailing as a fail-safe mechanism for efficient degradation of stalled nascent polypeptides.
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            NameFull: Osuna, Beatriz A.
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            NameFull: Frost, Adam
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              M: 07
              Text: 7/28/2017
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              Y: 2017
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