Similar Datasets
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.
2025-02-26 | GSE255779 | GEO
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.
2025-02-26 | GSE255783 | GEO
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.
2025-02-26 | GSE255780 | GEO
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.
2025-02-26 | GSE255781 | GEO
Project description:The integrated stress response finetunes 18S nonfunctional rRNA decay
| PRJNA1076510 | ENA
Project description:The integrated stress response finetunes 18S nonfunctional rRNA decay (DMS-MaPseq)
| PRJNA1076513 | ENA
Project description:The integrated stress response finetunes 18S nonfunctional rRNA decay (SHAP-MaP)
| PRJNA1076515 | ENA
Project description:The integrated stress response finetunes 18S nonfunctional rRNA decay (Ribo-Seq)
| PRJNA1076512 | ENA
Project description:The integrated stress response finetunes 18S nonfunctional rRNA decay (selective Ribo-Seq)
| PRJNA1076517 | ENA
Project description:In budding yeast, inactivating mutations within the 40S ribosomal subunit decoding center lead to 18S rRNA clearance by a quality control mechanism known as nonfunctional 18S rRNA decay (18S NRD). We previously showed that 18S NRD is functionally related to No-Go mRNA Decay (NGD), a pathway for clearing translation complexes stalled on aberrant mRNAs. Whereas the NGD factors Dom34p and Hbs1p contribute to 18S NRD, their genetic deletion (either singly or in combination) only partially stabilizes mutant 18S rRNA. Here we identify Asc1p (aka RACK1) and Rps3p, both stable 40S subunit components, as additional 18S NRD factors. Complete stabilization of mutant 18S rRNA in dom34Δ;asc1Δ and hbs1Δ;asc1Δ strains indicates the existence of two genetically separable 18S NRD pathways. A small region of the Rps3p C-terminal tail known to be subject to post-translational modification is also crucial for 18S NRD. We combine these findings with the effects of mutations in the 5' → 3' and 3' → 5' decay machinery to propose a model wherein multiple targeting and decay pathways kinetically contribute to 18S NRD.
| S-EPMC5689013 | biostudies-literature