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Molecular Functions of Conserved Developmentally-Regulated GTP-Binding Protein Drg1 in Translation

ABSTRACT: Molecular Functions of Conserved Developmentally-Regulated GTP-Binding Protein Drg1 in Translation

PROVIDER: PRJNA645425 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR12195277.fastq.gz	Fastqsanger.gz
	SRR12195278.fastq.gz	Fastqsanger.gz
	SRR12195279.fastq.gz	Fastqsanger.gz
	SRR12195280.fastq.gz	Fastqsanger.gz
	SRR12195281.fastq.gz	Fastqsanger.gz

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Molecular Functions of Conserved Developmentally-Regulated GTP-Binding Protein Drg1 in Translation

Project description:Developmentally-regulated GTP-binding (Drg) proteins are important for embryonic development, cell growth, proliferation, and differentiation. Despite their highly conserved nature, the functions of Drg proteins in translation are unknown. Here, we performed a wide analysis of ribosome dynamic in S.cerevisiae Rbg1, Rbg2 and Slh1 depleted cells using 5Pseq (Pelechano et al. 2015 PMID 26046441), which allows the study of ribosome dynamics by sequencing the 5' phoshporylated mRNA co-translational degradation itermediates. We demonstrate the yeast Drg ortholog, Rbg1, alleviates ribosome pausing at Arginine/Lysine-rich regions in mRNAs, and mainly targets genes related to ribonucleoprotein complex biogenesis and non-coding RNA processing pathways.

2020-07-11 | GSE154212 | GEO

Developmentally regulated requirement for the conserved transcription factor Grainy head in determining chromatin accessibility

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Developmentally Regulated GTP binding protein 1 (DRG1) controls microtubule dynamics.

Project description:The mitotic spindle, essential for segregating the sister chromatids into the two evolving daughter cells, is composed of highly dynamic cytoskeletal filaments, the microtubules. The dynamics of microtubules are regulated by numerous microtubule associated proteins. We identify here Developmentally regulated GTP binding protein 1 (DRG1) as a microtubule binding protein with diverse microtubule-associated functions. In vitro, DRG1 can diffuse on microtubules, promote their polymerization, drive microtubule formation into bundles, and stabilize microtubules. HeLa cells with reduced DRG1 levels show delayed progression from prophase to anaphase because spindle formation is slowed down. To perform its microtubule-associated functions, DRG1, although being a GTPase, does not require GTP hydrolysis. However, all domains are required as truncated versions show none of the mentioned activities besides microtubule binding.

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Structure and function of cancer-related developmentally regulated GTP-binding protein 1 (DRG1) is conserved between sponges and humans.

Project description:Cancer is a disease caused by errors within the multicellular system and it represents a major health issue in multicellular organisms. Although cancer research has advanced substantially, new approaches focusing on fundamental aspects of cancer origin and mechanisms of spreading are necessary. Comparative genomic studies have shown that most genes linked to human cancer emerged during the early evolution of Metazoa. Thus, basal animals without true tissues and organs, such as sponges (Porifera), might be an innovative model system for understanding the molecular mechanisms of proteins involved in cancer biology. One of these proteins is developmentally regulated GTP-binding protein 1 (DRG1), a GTPase stabilized by interaction with DRG family regulatory protein 1 (DFRP1). This study reveals a high evolutionary conservation of DRG1 gene/protein in metazoans. Our biochemical analysis and structural predictions show that both recombinant sponge and human DRG1 are predominantly monomers that form complexes with DFRP1 and bind non-specifically to RNA and DNA. We demonstrate the conservation of sponge and human DRG1 biological features, including intracellular localization and DRG1:DFRP1 binding, function of DRG1 in α-tubulin dynamics, and its role in cancer biology demonstrated by increased proliferation, migration and colonization in human cancer cells. These results suggest that the ancestor of all Metazoa already possessed DRG1 that is structurally and functionally similar to the human DRG1, even before the development of real tissues or tumors, indicating an important function of DRG1 in fundamental cellular pathways.

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Project description:Purine biosynthesis and metabolism, conserved in all living organisms, is essential for cellular energy homeostasis and nucleic acids synthesis. The de novo synthesis of purine precursors is under tight negative feedback regulation mediated by adenine and guanine nucleotides. We describe a new early-onset distinct neurodegenerative condition resulting from mutations in the adenosine monophosphate deaminase 2 gene (AMPD2). Patients have characteristic brain imaging features of pontocerebellar hypoplasia (PCH), due to loss of brainstem and cerebellar parenchyma. We found that AMPD2 plays an evolutionary conserved role in the maintenance of cellular guanine nucleotide pools by regulating the feedback inhibition of adenosine derivatives on de novo purine synthesis. AMPD2 deficiency results in defective GTP-dependent initiation of protein translation, which can be rescued by administration of purine precursors. These data suggest AMPD2-related PCH as a new potentially treatable early-onset neurodegenerative disease.

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Developmentally regulated sex differences in K48 polyubiquitination in the amygdala

Project description:This project examined if sex differences in K48 polyubiquitination in the amygdala were developmentally regulated. This used basolateral amygdala (BLA) samples collected from 4 and 9 week old male and female Sprague-Dawley rats.

2023-11-06 | PXD042021 | Pride

Murine C2C12 cells: GTP-stimulated cells vs. Control in SM

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AMPD2 Regulates GTP Synthesis and is Mutated in a Potentially-Treatable Neurodegenerative Brainstem Disorder

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