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Status |
Public on Feb 13, 2025 |
Title |
Grr1-mediated Ubp3 degradation is crucial for HAC1 mRNA translation and unfolded stress response in yeast [Riboseq] |
Organism |
Saccharomyces cerevisiae |
Experiment type |
Other
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Summary |
Ribosome ubiquitination induced by ribosome stalling is crucial for quality control pathways targeting mRNA, nascent polypeptides, and non-functional ribosomes. Besides quality control, Not4-mediated monoubiquitination of eS7A is crucial for the efficient translation of HAC1i mRNA in the unfolded protein response (UPR). In this study, we identified a novel E3 ligase, Grr1, an F-box protein component of the SCF ubiquitin ligase complex that is involved in Ubp3 degradation thereby HAC1i mRNA translation. Grr1 degrades Ubp3, a deubiquitinating enzyme of eS7A, under ER stress, thereby increasing eS7A ubiquitination, which facilitates HAC1i translation. Translation of HAC1i mRNA requires Grr1 and eS7 ubiquitination regardless of ER stress. ER stress-specific expression of Hac1 protein is ensured by the multi-step regulation of HAC1u mRNA, including localization on the ER membrane and stress-mediated splicing. Translation of HAC1i mRNA in UPR requires Grr1-mediated eS7 ubiquitination. More importantly, exon 1 of the HAC1i mRNA is crucial for translation activation by eS7 ubiquitination. Collectively, we propose that Grr1 upregulates eS7A monoubiquitination, thereby HAC1i translation and plays a crucial role in UPR.
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Overall design |
To investigate how ER stress affects translation, we performed ribosome profiling (Ribo-seq) of tunicamycin-treated W303 strains. The dataset includes 4 types of Ribo-seq samples in biological replicates (indicated as rep1 and rep2; 8 samples in total). Samples differ by the genotype (wild-type or grr1 deficient), and tunicamycin treatment time (0, 4 hr). We then calculated Translation efficiency (TE) using the read counts from Ribo-seq data and the read counts from RNA-seq data shown in another file. Besides, we analyzed ribosome footprints throughout HAC1i mRNA. For each genotype (wild-type or grr1 deficient), 0 hr data was compared against data of 4 hr data.
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Contributor(s) |
Sato N |
Citation missing |
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Submission date |
Mar 03, 2024 |
Last update date |
Feb 14, 2025 |
Contact name |
Nichika Sato |
E-mail(s) |
nicchisato2@g.ecc.u-tokyo.ac.jp
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Organization name |
The University of Tokyo
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Department |
The Institute of Medical Science
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Lab |
Division of RNA and Gene Regulation
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Street address |
4-6-1, Shirokanedai, Minato-ku
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City |
Tokyo |
ZIP/Postal code |
108-8639 |
Country |
Japan |
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Platforms (1) |
GPL26171 |
HiSeq X Ten (Saccharomyces cerevisiae) |
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Samples (8)
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GSM8123296 |
W303 strains, wild-type, Tunicamycin 0 h, replicate 1 [Ribo-seq] |
GSM8123297 |
W303 strains, wild-type, Tunicamycin 4 h, replicate 1 [Ribo-seq] |
GSM8123298 |
W303 strains, wild-type, Tunicamycin 0 h, replicate 2 [Ribo-seq] |
GSM8123299 |
W303 strains, wild-type, Tunicamycin 4 h, replicate 2 [Ribo-seq] |
GSM8123300 |
W303 strains, grr1-deficient, Tunicamycin 0 h, replicate 1 [Ribo-seq] |
GSM8123301 |
W303 strains, grr1-deficient, Tunicamycin 4 h, replicate 1 [Ribo-seq] |
GSM8123302 |
W303 strains, grr1-deficient, Tunicamycin 0 h, replicate 2 [Ribo-seq] |
GSM8123303 |
W303 strains, grr1-deficient, Tunicamycin 4 h, replicate 2 [Ribo-seq] |
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Relations |
BioProject |
PRJNA1083195 |
Supplementary file |
Size |
Download |
File type/resource |
GSE260736_RAW.tar |
65.6 Mb |
(http)(custom) |
TAR (of CSV, TXT) |
GSE260736_Riboseq.2_FC_WT_0_Ribovs_WT_4_Ribo.csv.gz |
318.7 Kb |
(ftp)(http) |
CSV |
GSE260736_Riboseq.2_FC_grr1_0_Ribovs_grr1_4_Ribo.csv.gz |
317.8 Kb |
(ftp)(http) |
CSV |
GSE260736_TE_FC_WT_0_vs_WT_4.csv.gz |
307.8 Kb |
(ftp)(http) |
CSV |
GSE260736_TE_FC_grr1_0_vs_grr1_4.csv.gz |
282.3 Kb |
(ftp)(http) |
CSV |
SRA Run Selector |
Raw data are available in SRA |
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