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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.

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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

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

Project description:Thymine DNA glycosylase (TDG) is a pivotal enzyme with dual roles in both genome maintenance and epigenetic regulation. TDG is involved in cytosine demethylation at CpG sites in DNA. Here we have used molecular modeling to delineate the lesion search and DNA base interrogation mechanisms of TDG. First, we examined the capacity of TDG to interrogate not only DNA substrates with 5-carboxyl cytosine modifications but also G:T mismatches and nonmismatched (A:T) base pairs using classical and accelerated molecular dynamics. To determine the kinetics, we constructed Markov state models. Base interrogation was found to be highly stochastic and proceeded through insertion of an arginine-containing loop into the DNA minor groove to transiently disrupt Watson-Crick pairing. Next, we employed chain-of-replicas path-sampling methodologies to compute minimum free energy paths for TDG base extrusion. We identified the key intermediates imparting selectivity and determined effective free energy profiles for the lesion search and base extrusion into the TDG active site. Our results show that DNA sculpting, dynamic glycosylase interactions, and stabilizing contacts collectively provide a powerful mechanism for the detection and discrimination of modified bases and epigenetic marks in DNA.

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Transcriptional responses of Acinetobacter baumannii ATCC 17978 to limiting iron availability

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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.

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Transcriptional responses of Acinetobacter baumannii ATCC 17978 to limiting iron availability

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