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The integrated stress response finetunes 18S nonfunctional rRNA decay (SHAP-MaP)

ABSTRACT: The integrated stress response finetunes 18S nonfunctional rRNA decay (SHAP-MaP)

PROVIDER: PRJNA1076515 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR27968000.fastq.gz	Fastqsanger.gz
	SRR27968001.fastq.gz	Fastqsanger.gz
	SRR27968002.fastq.gz	Fastqsanger.gz
	SRR27968003.fastq.gz	Fastqsanger.gz
	SRR27968004.fastq.gz	Fastqsanger.gz

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The integrated stress response finetunes 18S nonfunctional rRNA decay (SHAP-MaP)

Project description:18S nonfunctional rRNA decay (NRD) detects and eliminates translationally nonfunctional 18S rRNA. The underlying mechanisms associated with the detection and turnover of nonfunctional 18S rRNA remain elusive. While NRD has been identified and exclusively studied in Saccharomyces cerevisiae, it is unclear whether this quality control pathway exists in mammals. Here we demonstrate the conservation of 18S NRD in mammalian cells. Using genome-wide CRISPR genetic interaction screens, we identify two molecular events triggered by nonfunctional 18S rRNA— activation of the integrated stress response (ISR) and ubiquitination of ribosomal proteins elicited by GCN2 and RNF10, respectively. Selective ribosome profiling reveals nonfunctional 18S rRNA induces translation arrest at start sites. Biochemical analyses show that activation of the ISR limits translation initiation, attenuating collisions between scanning 43S preinitiation complexes and nonfunctional 80S ribosomes arrested at start sites. Thus, the ISR facilitates the turnover of nonfunctional 18S rRNA and 40S ribosomal proteins by RNF10-mediated ubiquitination. Altogether, these results establish a dynamic feedback mechanism by which cells finetune translation initiation to enable ribosome functionality surveillance through the GCN2-RNF10 axis.

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The integrated stress response finetunes 18S nonfunctional rRNA decay (Ribo-Seq)

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The integrated stress response finetunes 18S nonfunctional rRNA decay (DMS-MaPseq)

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The integrated stress response finetunes 18S nonfunctional rRNA decay (selective Ribo-Seq)

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The integrated stress response finetunes 18S nonfunctional rRNA decay

Project description:The integrated stress response finetunes 18S nonfunctional rRNA decay

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The integrated stress response finetunes 18S nonfunctional rRNA decay (Ribo-Seq)

Project description:The integrated stress response finetunes 18S nonfunctional rRNA decay (Ribo-Seq)

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The integrated stress response finetunes 18S nonfunctional rRNA decay (DMS-MaPseq)

Project description:The integrated stress response finetunes 18S nonfunctional rRNA decay (DMS-MaPseq)

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The integrated stress response regulates 18S nonfunctional rRNA decay in mammals

Project description:Abstract - 18S nonfunctional rRNA decay (NRD) detects and eliminates translationally nonfunctional 18S rRNA. While this process is critical for ribosome quality control, the mechanisms underlying nonfunctional 18S rRNA turnover remain elusive, particularly in mammals. Here, we show that mammalian 18S NRD initiates through the integrated stress response (ISR) via GCN2. Nonfunctional 18S rRNA induces translational arrest at start sites. Biochemical analyses demonstrate that ISR activation limits translation initiation and attenuates collisions between scanning 43S preinitiation complexes and stalled nonfunctional ribosomes. The ISR promotes 18S NRD and 40S ribosomal protein turnover by RNF10-mediated ubiquitination. Ultimately, RIOK3 binds the resulting ubiquitinated 40S subunits and facilitates 18S rRNA decay. Overall, mammalian 18S NRD acts through GCN2, followed by ubiquitin-dependent 18S rRNA degradation involving the ubiquitin E3 ligase RNF10 and the atypical protein kinase RIOK3. These findings establish a dynamic feedback mechanism by which the GCN2-RNF10-RIOK3 axis surveils ribosome functionality at the translation initiation step.

2024-12-09 | MSV000096620 | MassIVE

The integrated stress response finetunes 18S nonfunctional rRNA decay (selective Ribo-Seq)

Project description:The integrated stress response finetunes 18S nonfunctional rRNA decay (selective Ribo-Seq)

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The integrated stress response finetunes 18S nonfunctional rRNA decay

Project description:This SuperSeries is composed of the SubSeries listed below.

2025-02-26 | GSE255784 | GEO