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Disome and Trisome Profiling Reveal Genome-wide Targets of Ribosome Quality Control.
Mol Cell. 2020 Jun 27 [Online ahead of print]MC

Abstract

The ribosome-associated protein quality control (RQC) system that resolves stalled translation events is activated when ribosomes collide and form disome, trisome, or higher-order complexes. However, it is unclear whether this system distinguishes collision complexes formed on defective mRNAs from those with functional roles on endogenous transcripts. Here, we performed disome and trisome footprint profiling in yeast and found collisions were enriched on diverse sequence motifs known to slow translation. When 60S recycling was inhibited, disomes accumulated at stop codons and could move into the 3' UTR to reinitiate translation. The ubiquitin ligase and RQC factor Hel2/ZNF598 generally recognized collisions but did not induce degradation of endogenous transcripts. However, loss of Hel2 triggered the integrated stress response, via phosphorylation of eIF2α, thus linking these pathways. Our results suggest that Hel2 has a role in sensing ribosome collisions on endogenous mRNAs, and such events may be important for cellular homeostasis.

Authors+Show Affiliations

National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: nicholas.guydosh@nih.gov.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32615089

Citation

Meydan, Sezen, and Nicholas R. Guydosh. "Disome and Trisome Profiling Reveal Genome-wide Targets of Ribosome Quality Control." Molecular Cell, 2020.
Meydan S, Guydosh NR. Disome and Trisome Profiling Reveal Genome-wide Targets of Ribosome Quality Control. Mol Cell. 2020.
Meydan, S., & Guydosh, N. R. (2020). Disome and Trisome Profiling Reveal Genome-wide Targets of Ribosome Quality Control. Molecular Cell. https://doi.org/10.1016/j.molcel.2020.06.010
Meydan S, Guydosh NR. Disome and Trisome Profiling Reveal Genome-wide Targets of Ribosome Quality Control. Mol Cell. 2020 Jun 27; PubMed PMID: 32615089.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Disome and Trisome Profiling Reveal Genome-wide Targets of Ribosome Quality Control. AU - Meydan,Sezen, AU - Guydosh,Nicholas R, Y1 - 2020/06/27/ PY - 2019/10/21/received PY - 2020/04/07/revised PY - 2020/06/02/accepted PY - 2020/7/3/entrez PY - 2020/7/3/pubmed PY - 2020/7/3/medline KW - Gcn1 KW - Gcn2 KW - Gcn20 KW - Hcr1 KW - Hel2 KW - RQC KW - ZNF598 KW - recycling KW - ribosome collision KW - ribosome profiling JF - Molecular cell JO - Mol. Cell N2 - The ribosome-associated protein quality control (RQC) system that resolves stalled translation events is activated when ribosomes collide and form disome, trisome, or higher-order complexes. However, it is unclear whether this system distinguishes collision complexes formed on defective mRNAs from those with functional roles on endogenous transcripts. Here, we performed disome and trisome footprint profiling in yeast and found collisions were enriched on diverse sequence motifs known to slow translation. When 60S recycling was inhibited, disomes accumulated at stop codons and could move into the 3' UTR to reinitiate translation. The ubiquitin ligase and RQC factor Hel2/ZNF598 generally recognized collisions but did not induce degradation of endogenous transcripts. However, loss of Hel2 triggered the integrated stress response, via phosphorylation of eIF2α, thus linking these pathways. Our results suggest that Hel2 has a role in sensing ribosome collisions on endogenous mRNAs, and such events may be important for cellular homeostasis. SN - 1097-4164 UR - https://www.unboundmedicine.com/medline/citation/32615089/Disome_and_Trisome_Profiling_Reveal_Genome-wide_Targets_of_Ribosome_Quality_Control L2 - https://linkinghub.elsevier.com/retrieve/pii/S1097-2765(20)30395-6 DB - PRIME DP - Unbound Medicine ER -
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