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The E3 ubiquitin ligase and RNA-binding protein ZNF598 orchestrates ribosome quality control of premature polyadenylated mRNAs

Cryptic polyadenylation within coding sequences (CDS) triggers ribosome-associated quality control (RQC), followed by degradation of the aberrant mRNA and polypeptide, ribosome disassembly and recycling. Although ribosomal subunit dissociation and nascent peptide degradation are well-understood, the...

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Autores principales: Garzia, Aitor, Jafarnejad, Seyed Mehdi, Meyer, Cindy, Chapat, Clément, Gogakos, Tasos, Morozov, Pavel, Amiri, Mehdi, Shapiro, Maayan, Molina, Henrik, Tuschl, Thomas, Sonenberg, Nahum
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2017
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5504347/
https://www.ncbi.nlm.nih.gov/pubmed/28685749
http://dx.doi.org/10.1038/ncomms16056
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author Garzia, Aitor
Jafarnejad, Seyed Mehdi
Meyer, Cindy
Chapat, Clément
Gogakos, Tasos
Morozov, Pavel
Amiri, Mehdi
Shapiro, Maayan
Molina, Henrik
Tuschl, Thomas
Sonenberg, Nahum
author_facet Garzia, Aitor
Jafarnejad, Seyed Mehdi
Meyer, Cindy
Chapat, Clément
Gogakos, Tasos
Morozov, Pavel
Amiri, Mehdi
Shapiro, Maayan
Molina, Henrik
Tuschl, Thomas
Sonenberg, Nahum
author_sort Garzia, Aitor
collection PubMed
description Cryptic polyadenylation within coding sequences (CDS) triggers ribosome-associated quality control (RQC), followed by degradation of the aberrant mRNA and polypeptide, ribosome disassembly and recycling. Although ribosomal subunit dissociation and nascent peptide degradation are well-understood, the molecular sensors of aberrant mRNAs and their mechanism of action remain unknown. We studied the Zinc Finger Protein 598 (ZNF598) using PAR-CLIP and revealed that it cross-links to tRNAs, mRNAs and rRNAs, thereby placing the protein on translating ribosomes. Cross-linked reads originating from AAA-decoding tRNA(Lys)(UUU) were 10-fold enriched over its cellular abundance, and poly-lysine encoded by poly(AAA) induced RQC in a ZNF598-dependent manner. Encounter with translated polyA segments by ZNF598 triggered ubiquitination of several ribosomal proteins, requiring the E2 ubiquitin ligase UBE2D3 to initiate RQC. Considering that human CDS are devoid of >4 consecutive AAA codons, sensing of prematurely placed polyA tails by a specialized RNA-binding protein is a novel nucleic-acid-based surveillance mechanism of RQC.
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spelling pubmed-55043472017-07-14 The E3 ubiquitin ligase and RNA-binding protein ZNF598 orchestrates ribosome quality control of premature polyadenylated mRNAs Garzia, Aitor Jafarnejad, Seyed Mehdi Meyer, Cindy Chapat, Clément Gogakos, Tasos Morozov, Pavel Amiri, Mehdi Shapiro, Maayan Molina, Henrik Tuschl, Thomas Sonenberg, Nahum Nat Commun Article Cryptic polyadenylation within coding sequences (CDS) triggers ribosome-associated quality control (RQC), followed by degradation of the aberrant mRNA and polypeptide, ribosome disassembly and recycling. Although ribosomal subunit dissociation and nascent peptide degradation are well-understood, the molecular sensors of aberrant mRNAs and their mechanism of action remain unknown. We studied the Zinc Finger Protein 598 (ZNF598) using PAR-CLIP and revealed that it cross-links to tRNAs, mRNAs and rRNAs, thereby placing the protein on translating ribosomes. Cross-linked reads originating from AAA-decoding tRNA(Lys)(UUU) were 10-fold enriched over its cellular abundance, and poly-lysine encoded by poly(AAA) induced RQC in a ZNF598-dependent manner. Encounter with translated polyA segments by ZNF598 triggered ubiquitination of several ribosomal proteins, requiring the E2 ubiquitin ligase UBE2D3 to initiate RQC. Considering that human CDS are devoid of >4 consecutive AAA codons, sensing of prematurely placed polyA tails by a specialized RNA-binding protein is a novel nucleic-acid-based surveillance mechanism of RQC. Nature Publishing Group 2017-07-07 /pmc/articles/PMC5504347/ /pubmed/28685749 http://dx.doi.org/10.1038/ncomms16056 Text en Copyright © 2017, The Author(s) http://creativecommons.org/licenses/by/4.0/ Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Garzia, Aitor
Jafarnejad, Seyed Mehdi
Meyer, Cindy
Chapat, Clément
Gogakos, Tasos
Morozov, Pavel
Amiri, Mehdi
Shapiro, Maayan
Molina, Henrik
Tuschl, Thomas
Sonenberg, Nahum
The E3 ubiquitin ligase and RNA-binding protein ZNF598 orchestrates ribosome quality control of premature polyadenylated mRNAs
title The E3 ubiquitin ligase and RNA-binding protein ZNF598 orchestrates ribosome quality control of premature polyadenylated mRNAs
title_full The E3 ubiquitin ligase and RNA-binding protein ZNF598 orchestrates ribosome quality control of premature polyadenylated mRNAs
title_fullStr The E3 ubiquitin ligase and RNA-binding protein ZNF598 orchestrates ribosome quality control of premature polyadenylated mRNAs
title_full_unstemmed The E3 ubiquitin ligase and RNA-binding protein ZNF598 orchestrates ribosome quality control of premature polyadenylated mRNAs
title_short The E3 ubiquitin ligase and RNA-binding protein ZNF598 orchestrates ribosome quality control of premature polyadenylated mRNAs
title_sort e3 ubiquitin ligase and rna-binding protein znf598 orchestrates ribosome quality control of premature polyadenylated mrnas
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5504347/
https://www.ncbi.nlm.nih.gov/pubmed/28685749
http://dx.doi.org/10.1038/ncomms16056
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