Convergence of mammalian RQC and C-end rule proteolytic pathways via alanine tailing
Incompletely synthesized nascent chains obstructing large ribosomal subunits are targeted for degradation by ribosome-associated quality control (RQC). In bacterial RQC, RqcH marks the nascent chains with C-terminal alanine (Ala) tails that are directly recognized by proteasome-like proteases, where...
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| Hauptverfasser: | , , , , , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
April 27, 2021
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| In: |
Molecular cell
Year: 2021, Jahrgang: 81, Heft: 10, Pages: 2112-2122.e7 |
| ISSN: | 1097-4164 |
| DOI: | 10.1016/j.molcel.2021.03.004 |
| Online-Zugang: | Resolving-System, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.molcel.2021.03.004 Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S1097276521001726 
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| Verfasserangaben: | Anna Thrun, Aitor Garzia, Yu Kigoshi-Tansho, Pratik R. Patil, Charles S. Umbaugh, Teresa Dallinger, Jia Liu, Sylvia Kreger, Annarita Patrizi, Gregory A. Cox, Thomas Tuschl, and Claudio A.P. Joazeiro |
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| 245 | 1 | 0 | |a Convergence of mammalian RQC and C-end rule proteolytic pathways via alanine tailing |c Anna Thrun, Aitor Garzia, Yu Kigoshi-Tansho, Pratik R. Patil, Charles S. Umbaugh, Teresa Dallinger, Jia Liu, Sylvia Kreger, Annarita Patrizi, Gregory A. Cox, Thomas Tuschl, and Claudio A.P. Joazeiro |
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| 520 | |a Incompletely synthesized nascent chains obstructing large ribosomal subunits are targeted for degradation by ribosome-associated quality control (RQC). In bacterial RQC, RqcH marks the nascent chains with C-terminal alanine (Ala) tails that are directly recognized by proteasome-like proteases, whereas in eukaryotes, RqcH orthologs (Rqc2/NEMF [nuclear export mediator factor]) assist the Ltn1/Listerin E3 ligase in nascent chain ubiquitylation. Here, we study RQC-mediated proteolytic targeting of ribosome stalling products in mammalian cells. We show that mammalian NEMF has an additional, Listerin-independent proteolytic role, which, as in bacteria, is mediated by tRNA-Ala binding and Ala tailing. However, in mammalian cells Ala tails signal proteolysis indirectly, through a pathway that recognizes C-terminal degrons; we identify the CRL2KLHDC10 E3 ligase complex and the novel C-end rule E3, Pirh2/Rchy1, as bona fide RQC pathway components that directly bind to Ala-tailed ribosome stalling products and target them for degradation. As Listerin mutation causes neurodegeneration in mice, functionally redundant E3s may likewise be implicated in molecular mechanisms of neurodegeneration. | ||
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| 650 | 4 | |a ribosome-associated quality control | |
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