Tau drives translational selectivity by interacting with ribosomal proteins
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ABSTRACT:
PROVIDER: PRJNA496504 | ENA |
REPOSITORIES: ENA
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Project description:There is a fundamental gap in understanding the consequences of tau-ribosome interactions. Tau oligomers and filaments hinder protein synthesis in vitro, and they associate strongly with ribosomes in vivo. Here, we investigated the consequences of tau interactions with ribosomes in vivo and in human brain tissues to identify tau as a direct modulator of ribosomal selectivity. We performed microarrays and nascent proteomics to measure changes in protein synthesis using rTg4510 tau transgenic mice. We determined that tau expression differentially shifts the transcriptome and the proteome and that the synthesis of ribosomal proteins is reversibly dependent on tau levels. We further extended these results to human brains and show that tau pathologically interacts with ribosomal protein S6 (rpS6 or S6). Consequently, synthesis of ribosomal proteins coded by 5’TOP-mRNAs was reduced under tauopathic conditions in Alzheimer’s disease brains. Our data establish tau as a driver of RNA translation selectivity. Moreover, considering that regulation of protein synthesis is critical to learning and memory, aberrant tau-ribosome interactions in disease could explain the linkage between virtually every tauopathy and cognitive impairment and memory decline.
2019-03-30 | GSE121264 | GEO
Project description: Not available
| S-EPMC6426815 | biostudies-literature
Project description:The microtubule associating protien tau, (MAPT, tau) is a primary pathologic factor in a number of neurodegenerative disorders, including Alzheimer's Disease. Tau can interact with RNA. These interactions have been proposed as initiating factors for the formation of the pathological forms of tau noted in diseases. Additionally, it has been suggested that the m6A-methylation state of RNA is a factor in the association of RNA to tau. This study uses enhanced crosslinking immunoprecipitation (eCLIP) techniques to 1) identify, quantify, a sequence the RNA species interacting with the tau protein isolated from Alzheimers disease human hippocampal tissue, 2) identify, quantify, and sequence the methylated RNA in Alzheimer's disease human hippocampal tissue, and 3) to look for associations between the RNAs that interact with tau and RNA methylation status.
2026-06-30 | GSE326657 | GEO
Project description:The microtubule associating protien tau, (MAPT, tau) is a primary pathologic factor in a number of neurodegenerative disorders, including Alzheimer's Disease. Tau can interact with RNA. These interactions have been proposed as initiating factors for the formation of the pathological forms of tau noted in diseases. Additionally, it has been suggested that the m6A-methylation state of RNA is a factor in the association of RNA to tau. This study uses enhanced crosslinking immunoprecipitation (eCLIP) techniques to 1) identify, quantify, a sequence the RNA species interacting with the tau protein isolated from Alzheimers disease human hippocampal tissue, 2) identify, quantify, and sequence the methylated RNA in Alzheimer's disease human hippocampal tissue, and 3) to look for associations between the RNAs that interact with tau and RNA methylation status.
2026-06-30 | GSE299571 | GEO
Project description:The microtubule associating protien tau, (MAPT, tau) is a primary pathologic factor in a number of neurodegenerative disorders, including Alzheimer's Disease. Tau can interact with RNA. These interactions have been proposed as initiating factors for the formation of the pathological forms of tau noted in diseases. Additionally, it has been suggested that the m6A-methylation state of RNA is a factor in the association of RNA to tau. This study uses enhanced crosslinking immunoprecipitation (eCLIP) techniques to 1) identify, quantify, a sequence the RNA species interacting with the tau protein isolated from Alzheimers disease human hippocampal tissue, 2) identify, quantify, and sequence the methylated RNA in Alzheimer's disease human hippocampal tissue, and 3) to look for associations between the RNAs that interact with tau and RNA methylation status.
2026-06-30 | GSE299568 | GEO
Project description:The microtubule associating protien tau, (MAPT, tau) is a primary pathologic factor in a number of neurodegenerative disorders, including Alzheimer's Disease. Tau can interact with RNA. These interactions have been proposed as initiating factors for the formation of the pathological forms of tau noted in diseases. Additionally, it has been suggested that the m6A-methylation state of RNA is a factor in the association of RNA to tau. This study uses enhanced crosslinking immunoprecipitation (eCLIP) techniques to 1) identify, quantify, a sequence the RNA species interacting with the tau protein isolated from Alzheimers disease human hippocampal tissue, 2) identify, quantify, and sequence the methylated RNA in Alzheimer's disease human hippocampal tissue, and 3) to look for associations between the RNAs that interact with tau and RNA methylation status.
2026-06-30 | GSE299570 | GEO
Project description:High-resolution Ribosome Profiling Reveals Translational Selectivity in Bovine Preimplantation Embryo Development
| PRJNA805180 | ENA
Project description:High resolution polysome fractionation and low-input ribosome profiling of bovine oocytes and preimplantation embryos has enabled us to define the translational landscape of early embryo development at an unprecedented level. We systematically and comparatively analyzed the transcriptome, polysome- and nonpolysome-bound RNA profiles of bovine oocytes and early embryos at 2-, 8-cell, morula, and blastocyst stage, and defined four modes of translational selectivity in bovine preimplantation embryo development: i. selective translation of non-abundant mRNAs, ii. active translating highly expressed mRNAs, iii. Translationally suppressed abundant mRNAs, and iv. Monosomaly occupied mRNAs. A strong selection towards genes involved in mitochondrial function and metabolic pathways was found throughout bovine preimplantation development. We found translatome largely follows transcriptome at oocytes, followed by a marked translational control at 8-cell embryos, which is gradually synchronized at the morula and blastocyst stage. We identified important novel cellular/embryonic functional regulators that being utilized and prioritized for translation at each developmental stage, that accompanies little-known bovine embryonic developmental programming. Together, these data reveal a unique spatiotemporal translational regulation that accompanies bovine preimplantation development.
2022-10-01 | GSE196484 | GEO
Project description:Ribosomopathies are cell-type-specific pathologies related to a ribosomal protein (RP) gene insult. The 5q- syndrome is a somatic ribosomopathy linked to RPS14 gene haploinsufficiency and characterized by a prominent erythroid hypoplasia. Using quantitative proteomic, we show that GATA1 protein expression is low in shRPS14 cells in which ribosome quantities are diminished. Here, we investigated the cause of low GATA1 protein expression in limiting ribosome availability. A global analysis of translation in RPs deficiencies highlights the rules that drive translation selectivity. We demonstrate that in addition of the transcript length, a high codon adaptation index (CAI) and a highly structured 3’UTR are the key characteristics for a selective translation. An integrated analysis of transcriptome and proteome confirms that the post-transcriptional regulations of gene expression are directly linked to the criteria governing the translational selectivity. In particular, these criteria explain GATA1 translation default with unprecedented precision. More generally, the proteins that accumulate along normal erythropoiesis share the determinants of translation selectivity revealed by the conditions of limiting ribosome availability. We performed translatome expression profiling of cells infected with shRPS14 or shSCR
2020-04-28 | GSE124800 | GEO
Project description:RNA colocalizes with tau deposits in Alzheimer’s disease (AD) and other tauopathies, and drives tau aggregation in vitro. However, molecular details of RNA-tau interactions remain unclear, and in particular whether these interactions contribute to neurodegeneration. Previously, we determined a cryo-EM structure of fibrils of full-length tau bound to unfractionated mammalian RNA, revealing a small tau C-terminal core. Here, we present the cryo-EM structure of fibrils of full-length recombinant tau bound to unfractionated mammalian RNA and seeded by pathological tau fibrils extracted from the postmortem brain of an AD patient. This structure reveals an expanded tau C-terminal core with partial resemblance to AD tau fibrils. RNA sequencing identified 18S ribosomal RNA as the primary fibril-bound species, consistent with the well-documented link between pathological tau and ribosomal dysfunction in neurodegenerative diseases. Next, we determined the cryo-EM structure of fibrils of full-length recombinant tau bound to mammalian 18S ribosomal RNA, revealing a core that consists of the R2 to R4 repeat domains previously seen in several pathological polymorphic tau fibrils. All three of our recombinant RNA-tau fibrils dissolve upon RNase treatment, demonstrating that RNA is the molecular glue of these complexes. In the presence of different RNAs, tau fibrils adopt distinct folds, suggesting that RNA is a cofactor that shapes tau fibril polymorphism.
2026-02-17 | GSE319735 | GEO