Drosophila Trus, the orthologue of mammalian PDCD2L, is required for proper cell proliferation, larval developmental timing, and oogenesis DOI Creative Commons

Saeko Takada,

Bonnie J. Bolkan,

MaryJane O’Connor

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 26, 2024

Abstract Toys are us (Trus) is the Drosophila melanogaster ortholog of mammalian Programmed Cell Death 2-Like (PDCD2L), a protein that has been implicated in ribosome biogenesis, cell cycle regulation, and oncogenesis. In this study, we examined function Trus during development. CRISPR/Cas9 generated null mutations trus lead to partial embryonic lethality, significant larval developmental delay, complete pre-pupal lethality. mutant larvae, found decreased proliferation growth defects brain imaginal discs. Mapping relevant tissues for using RNAi rescue experiments revealed disc primarily responsible while lethality likely associated with faulty central nervous system (CNS) Examination molecular mechanism behind delay phenotype induce Xrp1-Dilp8 ribosomal stress-response growth-impaired discs, signaling pathway attenuates production hormone ecdysone prothoracic gland. Additional Tap-tagging mass spectrometry components complexes isolated from Kc cells identified Ribosomal subunit 2 (RpS2), which coded by string pearls (sop) Drosophila, Eukaryotic translation elongation factor 1 alpha (eEF1α1) as interacting factors. We discuss implication these findings respect similarity differences genetic phenotypes compared haplo-insufficiency produced heterozygosity mutants Minute genes other involved biogenesis. Authors Summary Ribosomes essential macromolecular machines required decoding mRNA make proteins, major biomolecules carry out all cellular functions. As such, their structural operational integrity critical organismal survival, disrupt proper stoichiometry or assembly ribosomes produce serious pathological consequences an organism’s development and/or adult life. The PDCD2L highly conserved yeast man, yet its overall requirement poorly understood. By examining , encodes homolog, demonstrate role cell-cycle regulation. Furthermore, disruption mitotically dividing tissue activates Xrp1-dilp8 stress response limits ecdysone, arthropod molting hormone, leading severe stages. These studies provide new insights on requirements assemble

Language: Английский

The Effects of Deregulated Ribosomal Biogenesis in Cancer DOI Creative Commons
Yiwei Lu, Shizhuo Wang, Yisheng Jiao

et al.

Biomolecules, Journal Year: 2023, Volume and Issue: 13(11), P. 1593 - 1593

Published: Oct. 30, 2023

Ribosomes are macromolecular ribonucleoprotein complexes assembled from RNA and proteins. Functional ribosomes arise the nucleolus, require ribosomal processing coordinated assembly of proteins (RPs), frequently hyperactivated to support requirement for protein synthesis during self-biosynthetic metabolic activities cancer cells. Studies have provided relevant information on targeted anticancer molecules involved in ribosome biogenesis (RiBi), as increased RiBi is characteristic many types cancer. The association between unlimited cell proliferation alterations specific steps has been highlighted a possible critical driver tumorigenesis metastasis. Thus, numerous regulators actors RiBi, particularly cancer, significantly affect rate quality and, ultimately, transcriptome generate associated proteome. Alterations cells activate nucleolar stress response-related pathways that play important roles cancer-targeted interventions immunotherapies. In this review, we focus Emphasis placed deregulation its secondary consequences, including changes synthesis, loss RPs, adaptive transcription translation, regulation, changes, impaired checkpoint.

Language: Английский

Citations

9
A new Drosophila melanogaster research resource: CRISPR-induced mutations for clonal analysis of fourth chromosome genes DOI Creative Commons
Bonnie M. Weasner, Brandon P. Weasner, Kevin R Cook

et al.

G3 Genes Genomes Genetics, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 13, 2025

As part of an ongoing effort to generate comprehensive resources for the experimental analysis fourth chromosome genes in Drosophila melanogaster, Fourth Chromosome Resource Project has used CRISPR mutagenesis with single guide RNAs isolate mutations 62 80 chromosome, protein-coding genes. These were induced on a bearing basal FRT insertion facilitate approaches involving FLP recombinase-induced mitotic recombination. To permit straightforward comparisons among mutant stocks, most generated isogenic chromosomes, which then crossed into common genetic background. Of 119 mutations, 84 are frameshift likely be null alleles, 29 small, in-frame deletions and 6 have yet characterized molecularly. The tested recessive lethal, female sterile visible phenotypes. Stable stocks been submitted repositories United States Japan public distribution.

Language: Английский

Citations

0
Corticosterone effects induced by stress and immunity and inflammation: mechanisms of communication DOI Creative Commons

Jingyu Xu,

B Wang,

Haiqing Ao

et al.

Frontiers in Endocrinology, Journal Year: 2025, Volume and Issue: 16

Published: March 20, 2025

The body instinctively responds to external stimuli by increasing energy metabolism and initiating immune responses upon receiving stress signals. Corticosterone (CORT), a glucocorticoid (GC) that regulates secretion along the hypothalamic-pituitary-adrenal (HPA) axis, mediates neurotransmission humoral regulation. Due widespread expression of receptors (GR), effects CORT are almost ubiquitous in various tissue cells. Therefore, on one hand, is molecular signal activates body’s system during other due chemical properties GCs, anti-inflammatory act as stabilizers control response stress. Inflammation manifestation activation. plays dual roles this process both promoting inflammation exerting As hormone, levels fluctuate with degree duration stress, determining its changes it induces. essential for resist diseases maintain homeostasis, imbalance being key factor development diseases. understanding role mechanisms action immunity crucial. This review addresses important issue summarizes interactions between system.

Language: Английский

Citations

0
Physiological and transcriptomic responses of silkworms to graphene oxide exposure DOI Creative Commons
Youchao Xin,

Jiawen Liang,

Chunjiu Ren

et al.

Ecotoxicology and Environmental Safety, Journal Year: 2024, Volume and Issue: 278, P. 116434 - 116434

Published: May 9, 2024

The growing use of nanomaterials has sparked significant interest in assessing the insect toxicities nanoparticles. silkworm, as an economically important insect, serves a promising model for studying how insects respond to harmful substances. Here, we conducted comprehensive investigation on impact graphene oxide (GO) silkworms using combination physiological and transcriptome analyses. GO can enter midguts posterior silk glands silkworms. High concentrations (> 25 mg/L) significantly (P < 0.01) inhibited larval growth. Additionally, 5 reduced cocooning rate, 15 hindered oviduct development egg laying increased reactive oxygen species content regulated catalase activity, suggesting that it may affect growth by regulating detoxification. data analysis showed 35 metabolism-related genes 20 ribosome biogenesis-related were differentially expressed response GO, their expression levels highly correlated. Finally, propose Ribosome biogenesis-Metabolic signaling network is involved responses GO. research provides new perspective molecular

Language: Английский

Citations

2
Maintenance of proteostasis by Drosophila Rer1 is essential for competitive cell survival and Myc-driven overgrowth DOI Creative Commons
Pranab Kumar Paul, Shruti Umarvaish, S. Bajaj

et al.

PLoS Genetics, Journal Year: 2024, Volume and Issue: 20(2), P. e1011171 - e1011171

Published: Feb. 26, 2024

Defects in protein homeostasis can induce proteotoxic stress, affecting cellular fitness and, consequently, overall tissue health. In various growing tissues, cell competition based mechanisms facilitate detection and elimination of these compromised, often referred to as 'loser', cells by the healthier neighbors. The precise connection between stress competitive survival remains largely elusive. Here, we reveal function an endoplasmic reticulum (ER) Golgi localized Rer1 regulation developing Drosophila wing epithelium. Our results show that loss leads PERK-mediated phosphorylation eukaryotic initiation factor 2α. Clonal analysis showed rer1 mutant are identified losers eliminated through competition. Interestingly, find levels upregulated upon Myc-overexpression causes overgrowth, albeit under high stress. suggest increased provide cytoprotection Myc-overexpressing alleviating thereby supporting Myc-driven overgrowth. summary, observations demonstrate acts a novel regulator proteostasis its role survival.

Language: Английский

Citations

1
The Beak of Eukaryotic Ribosomes: Life, Work and Miracles DOI Creative Commons
Sara Martín‐Villanueva, Carla V. Galmozzi, Carmen Ruger-Herreros

et al.

Biomolecules, Journal Year: 2024, Volume and Issue: 14(7), P. 882 - 882

Published: July 22, 2024

Ribosomes are not totally globular machines. Instead, they comprise prominent structural protrusions and a myriad of tentacle-like projections, which frequently made up ribosomal RNA expansion segments N- or C-terminal extensions proteins. This is more evident in higher eukaryotic ribosomes. One the most characteristic protrusions, present small subunits all three domains life, so-called beak, relevant for function regulation ribosome’s activities. During evolution, beak has transitioned from an structure (helix h33 16S rRNA) bacteria, to arrangement formed by proteins, eS10, eS12 eS31, smaller eukaryotes. In this review, we describe different functional properties beak. We discuss state-of-the-art concerning its composition significance, including other processes apparently related translation, dynamics assembly yeast human cells. Moreover, outline current view about relevance beak’s components diseases, especially ribosomopathies cancer.

Language: Английский

Citations

1
Integration of physiological and gene expression analyses to reveal biomarkers for protein dynamic mechanisms regulating higher growth and survival among larval oyster families (Crassostrea gigas) DOI Creative Commons
Ning Li, Tien-Chien Pan, Andrew W. Griffith

et al.

Aquaculture, Journal Year: 2023, Volume and Issue: 577, P. 739918 - 739918

Published: July 24, 2023

Language: Английский

Citations

1
Physical traits of supercompetitors in cell competition DOI Creative Commons

Logan C. Carpenter,

Shiladitya Banerjee

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 15, 2024

Cell competition is a fitness control mechanism in tissues, where less fit cells are eliminated to maintain tissue homeostasis. Two primary mechanisms of cell elimination have been identified studies: contact-dependent death and mechanical compression-driven apoptosis. While both occur their combined impact on population dynamics unclear. Here we develop cell-based computational model study between two types with differing physical properties. The integrates cellular mechanics cell-cycle dynamics, contact-induced apoptosis, extrusion via stress. Using this model, explored how differences traits influence competitive interactions. Our findings show that compressibility alone can drive competition, stiffer outcompeting softer ones otherwise identical populations. Surprisingly, mutations reduce stiffness, decreased contact inhibition proliferation, create “soft” super-competitive mutant. We demonstrate changes apoptosis sensitivity, adhesion, size significantly affect growth potential susceptibility Furthermore, mutant colonies require critical colony size, dependent compressibility, overtake the surrounding wild-type tissue. For below process stochastic, driven by protrusive finger-like instability interface promote invasion supercompetitors.

Language: Английский

Citations

0
Drosophila Trus, the orthologue of mammalian PDCD2L, is required for proper cell proliferation, larval developmental timing, and oogenesis DOI Creative Commons

Saeko Takada,

Bonnie J. Bolkan,

MaryJane O’Connor

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 26, 2024

Abstract Toys are us (Trus) is the Drosophila melanogaster ortholog of mammalian Programmed Cell Death 2-Like (PDCD2L), a protein that has been implicated in ribosome biogenesis, cell cycle regulation, and oncogenesis. In this study, we examined function Trus during development. CRISPR/Cas9 generated null mutations trus lead to partial embryonic lethality, significant larval developmental delay, complete pre-pupal lethality. mutant larvae, found decreased proliferation growth defects brain imaginal discs. Mapping relevant tissues for using RNAi rescue experiments revealed disc primarily responsible while lethality likely associated with faulty central nervous system (CNS) Examination molecular mechanism behind delay phenotype induce Xrp1-Dilp8 ribosomal stress-response growth-impaired discs, signaling pathway attenuates production hormone ecdysone prothoracic gland. Additional Tap-tagging mass spectrometry components complexes isolated from Kc cells identified Ribosomal subunit 2 (RpS2), which coded by string pearls (sop) Drosophila, Eukaryotic translation elongation factor 1 alpha (eEF1α1) as interacting factors. We discuss implication these findings respect similarity differences genetic phenotypes compared haplo-insufficiency produced heterozygosity mutants Minute genes other involved biogenesis. Authors Summary Ribosomes essential macromolecular machines required decoding mRNA make proteins, major biomolecules carry out all cellular functions. As such, their structural operational integrity critical organismal survival, disrupt proper stoichiometry or assembly ribosomes produce serious pathological consequences an organism’s development and/or adult life. The PDCD2L highly conserved yeast man, yet its overall requirement poorly understood. By examining , encodes homolog, demonstrate role cell-cycle regulation. Furthermore, disruption mitotically dividing tissue activates Xrp1-dilp8 stress response limits ecdysone, arthropod molting hormone, leading severe stages. These studies provide new insights on requirements assemble

Language: Английский

Citations

0