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: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE274722 | GEO | 2025/05/30

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Defective DcpS Decapping Manifests in Creatine Deficiency Syndrome and Neurological impairment

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

| PRJNA1147714 | ENA

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

Effect of acute creatine monohydrate supplementation on skeletal muscle transcriptome

2007-05-23 | GSE7877 | 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

Effect of acute creatine monohydrate supplementation on skeletal muscle transcriptome

Project description:Expression profiling of vastus lateralis muscle of young, healthy, non-obese men supplemented with creatine monohydrate vs. placebo for 10 days. Results identify transcriptional pathways activated in skeletal muscles as a result of acute creatine monohydrate supplementation. Keywords: Supplementation response. In a randomized, placebo-controlled, crossover, double-blind design, 12 young, healthy, non-obese men were supplemented with either a placebo or creatine monohydrate (loading phase, 20 g/d x 3 d; maintenance phase, 5 g/d x 7 d) for 10 d. Following a 28 day washout period, subjects were put on the alternate supplementation for 10 days. Muscle biopsies of the vastus lateralis were obtained and were assessed for global mRNA expression using cDNA microarrays.

2010-06-11 | E-GEOD-7877 | biostudies-arrayexpress

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

RNA-seq data of effects of DCPS inhibition in mouse AML cells (CALM/AF10) and in normal GMP cells. Overall mRNA profiles of CALM/AF10 (#1/#2) and MLL/AF9 (#1/#2).

Project description:Purpose: The goals of this study are to assess the possibility whether DCPS inhibition would impair pre-mRNA splicing in AML cells/normal GMP, and to assess overall effects of DCPS inhibition.

2018-11-22 | GSE107288 | GEO

Homo sapiens

Project description:The human decapping scavenger enzyme DcpS modulates microRNA turnover

| PRJNA285920 | ENA