Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA285920 | ENA |
REPOSITORIES: ENA
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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
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
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
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
Project description:Nudt3 is a mRNA Decapping Enzyme That Modulates Cell Migration
| PRJNA302638 | ENA
Project description:mRNA-decapping associated DcpS enzyme controls critical steps of neuronal development
| PRJNA726245 | ENA
Project description:Targeted Degradation of mRNA Decapping Enzyme DcpS by a VHL-Recruiting PROTAC
| PRJNA855935 | ENA
Project description:Gene expression profiling of immortalized human mesenchymal stem cells with hTERT/E6/E7 transfected MSCs. hTERT may change gene expression in MSCs. Goal was to determine the gene expressions of immortalized MSCs.
2010-09-25 | GSE24338 | GEO
Project description:Transcriptional profiling of human mesenchymal stem cells comparing normoxic MSCs cells with hypoxic MSCs cells. Hypoxia may inhibit senescence of MSCs during expansion. Goal was to determine the effects of hypoxia on global MSCs gene expression.
2011-02-19 | GSE20463 | GEO
Project description:Kynureninase is a member of a large family of catalytically diverse but structurally homologous pyridoxal 5'-phosphate (PLP) dependent enzymes known as the aspartate aminotransferase superfamily or alpha-family. The Homo sapiens and other eukaryotic constitutive kynureninases preferentially catalyze the hydrolytic cleavage of 3-hydroxy-l-kynurenine to produce 3-hydroxyanthranilate and l-alanine, while l-kynurenine is the substrate of many prokaryotic inducible kynureninases. The human enzyme was cloned with an N-terminal hexahistidine tag, expressed, and purified from a bacterial expression system using Ni metal ion affinity chromatography. Kinetic characterization of the recombinant enzyme reveals classic Michaelis-Menten behavior, with a Km of 28.3 +/- 1.9 microM and a specific activity of 1.75 micromol min-1 mg-1 for 3-hydroxy-dl-kynurenine. Crystals of recombinant kynureninase that diffracted to 2.0 A were obtained, and the atomic structure of the PLP-bound holoenzyme was determined by molecular replacement using the Pseudomonas fluorescens kynureninase structure (PDB entry 1qz9) as the phasing model. A structural superposition with the P. fluorescens kynureninase revealed that these two structures resemble the "open" and "closed" conformations of aspartate aminotransferase. The comparison illustrates the dynamic nature of these proteins' small domains and reveals a role for Arg-434 similar to its role in other AAT alpha-family members. Docking of 3-hydroxy-l-kynurenine into the human kynureninase active site suggests that Asn-333 and His-102 are involved in substrate binding and molecular discrimination between inducible and constitutive kynureninase substrates.
| S-EPMC2531291 | biostudies-literature