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Rules governing translation selectivity under limiting ribosome availability

ABSTRACT: Rules governing translation selectivity under limiting ribosome availability

PROVIDER: PRJNA513511 | ENA |

REPOSITORIES: ENA

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Rules governing translation selectivity under limiting ribosome availability

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

Molecular rules governing de novo methylation in cancer

Project description:De novo methylation of CpG islands is seen in many tumors, but the general rules governing this process are not known. By analyzing DNA from tumors, as well as normal tissues, and by utilizing a wide range of published data, we have been able to identify a well-defined set of tumor targets, each of which has its own M-bM-^@M-^\coefficientM-bM-^@M-^] of methylation that is largely determined by its inherent relative ability to recruit the polycomb complex. This pattern is initially formed by a slow process of de novo methylation that occurs during aging and then undergoes expansion early in tumorigenesis, where it may play a role as an inhibitor of development-associated gene activation. We also demonstrate that DNA methylation patterns can be used to diagnose the primary tissue source of tumor metastases. CpG-methylated genomic DNA was enriched using a methyl-DNA immunoprecipitation (mDIP) assay. DNA from the input and bound (enriched) DNA for each sample were labeled and hybridized on the array to define the methylation state of each region.

2014-03-26 | E-GEOD-38142 | biostudies-arrayexpress

Molecular rules governing de novo methylation in cancer

Project description:De novo methylation of CpG islands is seen in many tumors, but the general rules governing this process are not known. By analyzing DNA from tumors, as well as normal tissues, and by utilizing a wide range of published data, we have been able to identify a well-defined set of tumor targets, each of which has its own “coefficient” of methylation that is largely determined by its inherent relative ability to recruit the polycomb complex. This pattern is initially formed by a slow process of de novo methylation that occurs during aging and then undergoes expansion early in tumorigenesis, where it may play a role as an inhibitor of development-associated gene activation. We also demonstrate that DNA methylation patterns can be used to diagnose the primary tissue source of tumor metastases.

2014-03-26 | GSE38142 | GEO

High-throughput functional analysis of lncRNA core promoters elucidates rules governing tissue specificity

Project description:High-throughput functional analysis of lncRNA core promoters elucidates rules governing tissue specificity

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Integrated analyses of translatome and proteome identify the rules of translation selectivity in RPS14-deficient

Project description:Integrated analyses of translatome and proteome identify the rules of translation selectivity in RPS14-deficient

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Rules and mechanisms governing G protein coupling selectivity of GPCRs.

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Uncovering universal rules governing the selectivity of the archetypal DNA glycosylase TDG.

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Substrate selectivity for semisynthetic CK2 proteins

Project description:This SuperSeries is composed of the following subset Series: GSE33149: Substrate selectivity for semisynthetic CK2 proteins with various posttranslational modifications GSE33150: Substrate selectivity for semisynthetic CK2 proteins with Pin1 Refer to individual Series

2011-10-24 | E-GEOD-33151 | biostudies-arrayexpress

Glutamine addicted myeloma cells inhibits osteoblastic differentiation of bone marrow mesenchymal stromal cells limiting asparagine availability.

Project description:Glutamine addicted myeloma cells inhibits osteoblastic differentiation of bone marrow mesenchymal stromal cells limiting asparagine availability.

| PRJNA616375 | ENA

A Workflow for Transcriptome-wide Assessment of Antisense Oligonucleotide Selectivity

Project description:Antisense oligonucleotides (ASOs) designed to recruit RNase H1 (gapmer ASOs) have been used successfully to downregulate the expression of therapeutic targets. Gapmer ASOs can be identified that selectively reduce the expression of transcripts containing the perfectly complementary intended ASO target site without affecting the expression of unintended transcripts (selective ASOs). However, ASOs can also be identified that reduce the expression of unintended transcripts with target sites that are not perfectly complementary to the ASO (non-selective ASOs). Currently, the understanding of in silico rules for predicting off-targets is suboptimal. In order to determine the selectivity of gapmer ASOs, we therefore developed an experimental workflow called Concentration-Response Digital Gene Expression (CR-DGE). In CR-DGE, ASO treatment is performed at increasing concentrations and the effect on the transcriptome is measured using 3’Tag-Seq. Expression data are then analyzed to identify genes with concentration-responsive knockdown. We demonstrate that CR-DGE identifies ASO concentration-responsive genes with high reproducibility and greater sensitivity than conventional single-concentration assays. Applying CR-DGE to a panel of gapmer ASOs identifies ASOs with a range of selectivity. These results demonstrate that CR-DGE can be used effectively to assess the selectivity of gapmer ASOs, offering a valuable tool for research and therapeutic development.

2025-11-24 | GSE293987 | GEO

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