4EHP and GIGYF1/2 induce translation-coupled messenger RNA decay [Wildtype and ZNF598-null]
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA627881 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR11604768_1.fastq.gz | Fastqsanger.gz | |||
| SRR11604768_2.fastq.gz | Fastqsanger.gz | |||
| SRR11604769_1.fastq.gz | Fastqsanger.gz | |||
| SRR11604769_2.fastq.gz | Fastqsanger.gz | |||
| SRR11604770_1.fastq.gz | Fastqsanger.gz |
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Project description:Although canonical mRNA degradation is generally recognized to be translation dependent, our understanding of the molecular events that coordinate ribosome movement with the decay machinery is still limited. Here, we show that the 4EHP–GIGYF1/2 complex triggers co-translational mRNA decay as a result of altered ribosome activity during elongation. Human cells lacking 4EHP and GIGYF1 and 2 proteins accumulate transcripts known to be degraded in a translation dependent manner or with prominent ribosome pausing. These include mRNAs encoding secretory and membrane-bound proteins or specific tubulin isotypes, among others. 4EHP–GIGYF1/2 fails to reduce target mRNA levels in the absence of ribosome stalling or upon disruption of its interaction with the cap structure, DDX6 and a GYF domain-associated protein. Our studies reveal how a repressor complex linked to neurological disorders minimizes the protein output of a subset of mRNAs.
2020-10-06 | GSE149279 | GEO
Project description:4EHP and GIGYF1/2 induce translation-coupled messenger RNA decay
| PRJNA605114 | ENA
Project description:Although canonical mRNA degradation is generally recognized to be translation dependent, our understanding of the molecular events that coordinate ribosome movement with the decay machinery is still limited. Here, we show that the 4EHP–GIGYF1/2 complex triggers co-translational mRNA decay as a result of altered ribosome activity during elongation. Human cells lacking 4EHP and GIGYF1 and 2 proteins accumulate transcripts known to be degraded in a translation dependent manner or with prominent ribosome pausing. These include mRNAs encoding secretory and membrane-bound proteins or specific tubulin isotypes, among others. 4EHP–GIGYF1/2 fails to reduce target mRNA levels in the absence of ribosome stalling or upon disruption of its interaction with the cap structure, DDX6 and a GYF domain-associated protein. Our studies reveal how a repressor complex linked to neurological disorders minimizes the protein output of a subset of mRNAs.
2020-10-23 | GSE144841 | GEO
Project description:Quality control of translation is crucial for maintaining cellular and organismal homeostasis. Obstacles in translation elongation induce ribosome collision, which is monitored by multiple sensor mechanisms in eukaryotes. The E3 ubiquitin ligase Znf598 recognizes collided ribosomes, triggering ribosome-associated quality control (RQC) to rescue stalled ribosomes and no-go decay (NGD) to degrade stall-prone mRNAs. However, the impact of RQC and NGD on maintaining the translational homeostasis of endogenous mRNAs has remained unclear. In this study, we investigated the endogenous substrate mRNAs of NGD during the maternal-to-zygotic transition (MZT) of zebrafish development. RNA-Seq analysis of zebrafish znf598 mutant embryos revealed that Znf598 downregulates mRNAs encoding the C2H2-type zinc finger domain (C2H2-ZF) during the MZT. Reporter assays and disome profiling indicated that ribosomes stall and collide while translating tandem C2H2-ZFs, leading to mRNA degradation by Znf598. Our results suggest that NGD maintains the quality of the translatome by mitigating the risk of ribosome collision at the abundantly present C2H2-ZF sequences in the vertebrate genome.
2024-10-03 | GSE236144 | GEO
Project description:Quality control of translation is crucial for maintaining cellular and organismal homeostasis. Obstacles in translation elongation induce ribosome collision, which is monitored by multiple sensor mechanisms in eukaryotes. The E3 ubiquitin ligase Znf598 recognizes collided ribosomes, triggering ribosome-associated quality control (RQC) to rescue stalled ribosomes and no-go decay (NGD) to degrade stall-prone mRNAs. However, the impact of RQC and NGD on maintaining the translational homeostasis of endogenous mRNAs has remained unclear. In this study, we investigated the endogenous substrate mRNAs of NGD during the maternal-to-zygotic transition (MZT) of zebrafish development. RNA-Seq analysis of zebrafish znf598 mutant embryos revealed that Znf598 downregulates mRNAs encoding the C2H2-type zinc finger domain (C2H2-ZF) during the MZT. Reporter assays and disome profiling indicated that ribosomes stall and collide while translating tandem C2H2-ZFs, leading to mRNA degradation by Znf598. Our results suggest that NGD maintains the quality of the translatome by mitigating the risk of ribosome collision at the abundantly present C2H2-ZF sequences in the vertebrate genome.
2024-10-03 | GSE236143 | GEO
Project description:Global alteration of transcript decay rates upon ZNF598 knockdown
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Project description:We calculated half-life of transcripts in HEK293T cells expressing control or ZNF598-targeting shRNA.
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Project description:Mammalian body temperature oscillates with the time of the day and is altered in diverse pathological conditions. We recently identified a body temperature-sensitive thermometer-like kinase, which alters SR protein phosphorylation and thereby globally controls alternative splicing (AS). AS can generate unproductive variants which are recognized and degraded by diverse mRNA decay pathways – including nonsense-mediated decay (NMD). Here we show extensive coupling of body temperature-controlled AS to mRNA decay, leading to global control of temperature-dependent gene expression (GE). Temperature-controlled, decay-inducing splicing events are evolutionarily conserved and pervasively found within RNA-binding proteins, including most SR proteins. AS-coupled poison exon inclusion is essential for rhythmic GE of SR proteins and has a global role in establishing temperature-dependent rhythmic GE profiles, both, in mammals under circadian body temperature cycles and in plants in response to ambient temperature changes. Together, these data identify body temperature-driven AS coupled mRNA decay as an evolutionary ancient, core clock-independent mechanism to generate rhythmic GE.
2020-11-01 | GSE158882 | GEO
Project description:Various messenger RNA (mRNA) decay mechanisms play major roles in controlling mRNA quality and quantity in eukaryotic organisms under different conditions. While it is known that the recently discovered co-translational mRNA decay (CTRD), the mechanism that allows mRNAs to be degraded while still being actively translated, is prevalent in yeast, human, and various angiosperms, the regulation of this decay mechanism is less well studied. Moreover, it is still unclear whether this decay mechanism plays any roles in regulation of specific physiological processes in eukaryotes. Here, by re-analyzing the publicly available polysome profiling or ribosome footprinting and degradome sequencing datasets, we discovered that highly translated mRNAs tend to have lower co-translational decay levels. Based on this finding, we then identified Pelota and Hbs1, the translation-related ribosome rescue factors, as suppressors of co-translational mRNA decay in Arabidopsis. Furthermore, we found that Pelota and Hbs1 null mutants have lower germination rates compared to the wild type plants, implying that proper regulation of co-translational mRNA decay is essential for normal developmental processes. In total, our study provides further insights into the regulation of CTRD in Arabidopsis and demonstrates that this decay mechanism does play important roles in Arabidopsis physiological processes.
2023-12-31 | GSE247329 | GEO
Project description:Various messenger RNA (mRNA) decay mechanisms play major roles in controlling mRNA quality and quantity in eukaryotic organisms under different conditions. While it is known that the recently discovered co-translational mRNA decay (CTRD), the mechanism that allows mRNAs to be degraded while still being actively translated, is prevalent in yeast, human, and various angiosperms, the regulation of this decay mechanism is less well studied. Moreover, it is still unclear whether this decay mechanism plays any roles in regulation of specific physiological processes in eukaryotes. Here, by re-analyzing the publicly available polysome profiling or ribosome footprinting and degradome sequencing datasets, we discovered that highly translated mRNAs tend to have lower co-translational decay levels. Based on this finding, we then identified Pelota and Hbs1, the translation-related ribosome rescue factors, as suppressors of co-translational mRNA decay in Arabidopsis. Furthermore, we found that Pelota and Hbs1 null mutants have lower germination rates compared to the wild type plants, implying that proper regulation of co-translational mRNA decay is essential for normal developmental processes. In total, our study provides further insights into the regulation of CTRD in Arabidopsis and demonstrates that this decay mechanism does play important roles in Arabidopsis physiological processes.
2023-12-31 | GSE247328 | GEO