4EHP and GIGYF1/2 induce translation-coupled messenger RNA decay
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ABSTRACT:
PROVIDER: PRJNA605114 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR12879057.fastq.gz | Fastqsanger.gz | |||
| SRR12879058_1.fastq.gz | Fastqsanger.gz | |||
| SRR12879058_2.fastq.gz | Fastqsanger.gz | |||
| SRR12879059_1.fastq.gz | Fastqsanger.gz | |||
| SRR12879059_2.fastq.gz | Fastqsanger.gz |
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Project description:4EHP and GIGYF1/2 induce translation-coupled messenger RNA decay [Wildtype and ZNF598-null]
| PRJNA627881 | 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: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:N6-methyladenosine (m6A) is the most abundant internal messenger (mRNA) modification in mammalian mRNA. This modification is reversible and non-stoichiometric, which potentially adds an additional layer of variety and dynamic control of mRNA metabolism. The m6A-modified mRNA can be selectively recognized by the YTH family “reader” proteins. The preferential binding of m6A-containing mRNA by YTHDF2 is known to reduce the stability of the target transcripts; however, the exact effects of m6A on translation has yet to be elucidated. Here we show that another m6A reader protein, YTHDF1, promotes ribosome loading of its target transcripts. YTHDF1 forms a complex with translation initiation factors to elevate the translation efficiency of its bound mRNA. In a unified mechanism of translation control through m6A, the YTHDF2-mediated decay controls the lifetime of target transcripts; whereas, the YTHDF1-based translation promotion increases the translation efficiency to ensure effective protein production from relatively short-lived transcripts that are marked by m6A. PAR-CLIP and RIP was used to identify YTHDF1 binding sites followed by ribosome profling and RNA seq to assess the consequences of YTHDF1 siRNA knock-down
2015-06-09 | E-GEOD-63591 | biostudies-arrayexpress
Project description:N6-methyladenosine (m6A) is the most abundant internal messenger (mRNA) modification in mammalian mRNA. This modification is reversible and non-stoichiometric, which potentially adds an additional layer of variety and dynamic control of mRNA metabolism. The m6A-modified mRNA can be selectively recognized by the YTH family “reader” proteins. The preferential binding of m6A-containing mRNA by YTHDF2 is known to reduce the stability of the target transcripts; however, the exact effects of m6A on translation has yet to be elucidated. Here we show that another m6A reader protein, YTHDF1, promotes ribosome loading of its target transcripts. YTHDF1 forms a complex with translation initiation factors to elevate the translation efficiency of its bound mRNA. In a unified mechanism of translation control through m6A, the YTHDF2-mediated decay controls the lifetime of target transcripts; whereas, the YTHDF1-based translation promotion increases the translation efficiency to ensure effective protein production from relatively short-lived transcripts that are marked by m6A.
2015-06-09 | GSE63591 | GEO
Project description:Current models of mRNA turnover indicate that cytoplasmic degradation is coupled with translation. However, our understanding of the molecular events that coordinate ribosome transit with the mRNA decay machinery is still limited. Here, we show that 4EHP-GIGYF1/2 complexes trigger co-translational mRNA decay. Human cells lacking these proteins accumulate mRNAs with prominent ribosome pausing. They include, among others, transcripts encoding secretory and membrane-bound proteins or tubulin subunits. In addition, 4EHP-GIGYF1/2 complexes fail to reduce mRNA levels in the absence of ribosome stalling or upon disruption of their interaction with the cap structure, DDX6, and ZNF598. We further find that co-translational binding of GIGYF1/2 to the mRNA marks transcripts with perturbed elongation to decay. Our studies reveal how a repressor complex linked to neurological disorders minimizes the protein output of a subset of mRNAs.
| S-EPMC8984682 | biostudies-literature
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
Project description:NOT proteins in co-translation decay
| PRJNA706755 | ENA
Project description:N6-methyladenosine (m6A) is the most abundant internal modification in eukaryotic messenger RNAs (mRNAs), and plays important roles in cell differentiation and organism development. It regulates multiple steps throughout the RNA life cycle including RNA processing, translation, and metabolism, via the recognition by selective binding proteins. In cytoplasm, m6A binding protein YTHDF1 facilitates translation of m6A-modified mRNAs, and YTHDF2 accelerates the decay of m6A-modified transcripts. The biological function of YTHDF3, another cytoplasmic m6A binder of the YTH domain family, remains unknown. Here, we report that YTHDF3 promotes protein synthesis in synergy with YTHDF1, and affects methylated mRNA decay mediated by YTHDF2. Cells deficient in all of YTHDF proteins experience the most dramatic accumulation of the m6A-methylated transcripts. These results indicate that in cytoplasm, YTHDF proteins act in an integrated and cooperative network to accelerate metabolism of m6A-modified mRNAs. The combinative and dynamic nature of YTHDF proteins may collectively impact fundamental biological processes and diseases related to m6A RNA methylation.
2016-09-15 | GSE86214 | GEO