Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Defective DcpS Decapping Manifests in Creatine Deficiency Syndrome and Neurological impairment

ABSTRACT: Defective DcpS Decapping Manifests in Creatine Deficiency Syndrome and Neurological impairment

PROVIDER: PRJNA1147714 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other
	SRR30224384_1.fastq.gz	Fastqsanger.gz
	SRR30224384_2.fastq.gz	Fastqsanger.gz
	SRR30224385_1.fastq.gz	Fastqsanger.gz
	SRR30224385_2.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 7

Similar Datasets

Defective DcpS Decapping Manifests in Creatine Deficiency Syndrome and Neurological impairment

Project description:Biallelic mutations in the DCPS gene that disrupt the decapping activity of the DcpS scavenger decapping enzyme lead to neurodevelopmental deficiencies and intellectual disability. However, how the neurogenesis defects arise in these individuals remains unknown. Here we show that cells derived from DCPS mutant individuals have a metabolic deficiency in their creatine biosynthetic pathway. The cells possess reduced levels of creatine and a corresponding elevation of the creatine precursor, guanidinoacetate (GAA), due to reduced levels of guanidinoacetate methyltransferase mRNA and protein. Importantly, the compromised neurogenesis as well as neurite outgrowth observed in DcpS mutant induced pluripotent stem cell differentiation into neurons was reversed upon supplementation of creatine monohydrate into the culture medium. These findings suggest creatine deficiency as the underlying etiology of the neurogenetic defect in DcpS mutant cells and a potential driver of the neurological deficienciesin affected individuals.

2025-05-30 | GSE274722 | GEO

The human decapping scavenger enzyme DcpS modulates microRNA turnover

Project description:The decapping scavenger enzyme DcpS is known for its role in hydrolyzing the cap structure following mRNA degradation. Recently, we discovered a new function in miRNA degradation activation for the ortholog of DcpS in C. elegans. Here we show that human DcpS conserves its role in miRNA turnover. In human cells, DcpS is a nucleocytoplasmic shuttling protein and that DcpS activates miRNA degradation independently of its scavenger decapping activity in the cytoplasmic compartment. We also demonstrate that this new function for DcpS requires the contribution of the 5’-3’ exonuclease Xrn2. Our findings support a conserved role of DcpS as a modulator of miRNA turnover in animals.

2016-05-23 | GSE69591 | GEO

mRNA-decapping associated DcpS enzyme controls critical steps of neuronal development

Project description:Homozygous mutations in the gene encoding the scavenger mRNA-decapping enzyme, DcpS, have been shown to underlie developmental delay and intellectual disability. Intellectual disability is associated with both abnormal neocortical development and mRNA metabolism. However, the role of DcpS and its scavenger decapping activity in proper neuronal development is unknown. Here, we show that differentiation of human induced pluripotent stem cell derived neurons, from patients with a DcpS mutation, are impaired and have compromised neurite outgrowth. Moreover, misexpression of DcpS in developing mouse neocortex revealed that DcpS is required for the multipolar morphology acquisition, neurite outgrowth and identity of developing neocortical glutamatergic neurons in the mouse brain. Collectively, these findings demonstrate the scavenger mRNA decapping activity contributes to multiple pivotal roles in neurodevelopment, and further corroborate that mRNA metabolism and neocortical pathologies are associated with intellectual disability.

2022-04-06 | GSE173603 | GEO

Targeted Degradation of mRNA Decapping Enzyme DcpS by a VHL-Recruiting PROTAC

Project description:The RNA decapping scavenger, DcpS, has recently been identified as a dependency in acute myeloid leukemia. The potent DcpS inhibitor RG3039 attenuates AML cell viability, and shRNA knockdown of DcpS is also antiproliferative. Importantly, DcpS was found to be non-essential in normal human hematopoietic cells, which opens a therapeutic window for AML treatment by modulation of DcpS. Considering this strong dependence of AML cell lines on DcpS, we wanted to explore PROTAC-mediated degradation as an alternative strategy to modulate DcpS activity. Herein, we report the development of JCS-1, the first PROTAC capable of degrading an mRNA-decapping enzyme. JCS-1 non-covalently binds DcpS with an RG3039-based warhead and recruits the E3 ligase VHL, which induces potent, rapid, and sustained DcpS degradation in several AML cell lines. JCS-1 will serve as a chemical biology tool to interrogate DcpS function in different cellular contexts and may be an applicable strategy for the treatment of AML and other DcpS-dependent genetic disorders.

2022-07-08 | GSE207500 | GEO

mRNA-decapping associated DcpS enzyme controls critical steps of neuronal development

Project description:mRNA-decapping associated DcpS enzyme controls critical steps of neuronal development

| PRJNA726245 | ENA

Nanopore RNA sequencing in S. cerevisiae strains defective for decapping and deadenylation

Project description:RNA turnover in eukaryotes is triggered by decapping, believed to be activated mostly after deadenylation. To investigate simultaneous changes in RNA levels and poly(A) tail size we performed Nanopore RNA sequencing on total RNA extracted from S. cerevisiae strains in which the decapping enzyme Dcp2, or the deadenylation factors Ccr4 and Pop2 were depleted through an inducible degron system. Two fully independent replicate experiments were performed for wild type and the two mutant conditions.

2022-10-01 | GSE211782 | GEO

Targeted Degradation of mRNA Decapping Enzyme DcpS by a VHL-Recruiting PROTAC

Project description:Targeted Degradation of mRNA Decapping Enzyme DcpS by a VHL-Recruiting PROTAC

| PRJNA855935 | ENA

Nudt3 is a mRNA Decapping Enzyme That Modulates Cell Migration

Project description:The Dcp2 and Nudt16 Nudix hydrolases, are mRNA decapping enzymes that preferentially modulate stability of a subset of mRNAs. Here we report Nudt3 is a third Nudix protein that possess mRNA decapping activity in cells and is a modulator of cell migration in MCF-7 breast cancer cells. Genome-wide analysis of Nudt3 compromised cells identified increases in mRNAs involved in cell motility including integrin Î²6, lipocalin-2 and fibronectin. The increase in mRNA levels was dependent on Nudt3 decapping activity where integrin Î²6 and lipocalin-2 were modulated directly through mRNA stability, while fibronectin was indirectly controlled. Moreover, increased cell migration observed in Nudt3 depleted cells was mediated through the extracellular integrin Î²6 and fibronectin protein nexus. We conclude, Nudt3 is an mRNA decapping enzyme that orchestrates expression of a subset of mRNAs to modulate cell migration and further substantiates the existence of multiple decapping enzymes functioning in distinct cellular pathways in mammals. Stably transformed MCF-7 cell lines constitutively expressing either a short hairpin RNA (shRNA) directed against Nudt3 (Nudt3KD) or a non-targeted control shRNA (ConKD) were used, with three replicate cultures used per group (n=3).

2016-07-21 | E-GEOD-75146 | biostudies-arrayexpress

Metabolic reprogramming of macrophage polarization by creatine [ATAC-seq]

Project description:We found that the creatine metabolic pathway was differentially regulated under M1 versus M2 polarizing conditions. In return, creatine could suppress M1 by blocking STAT1 tyrosine phosphorylation while promote M2 by sustaining chromatin accessibility of specific gene loci.

2019-08-06 | GSE110403 | GEO

Metabolic reprogramming of macrophage polarization by creatine [RNA-seq]

2019-08-06 | GSE110395 | GEO