Exosomal mediators in sepsis and inflammatory organ injury: unraveling the role of exosomes in intercellular crosstalk and organ dysfunction

Military Medical Research, Journal Year: 2024, Volume and Issue: 11(1)

Published: April 22, 2024

Abstract Sepsis, a severe systemic inflammatory response to infection, remains leading cause of morbidity and mortality worldwide. Exosomes, as mediators intercellular communication, play pivotal role in the pathogenesis sepsis through modulating immune responses, metabolic reprogramming, coagulopathy, organ dysfunction. This review highlights emerging significance exosomes these processes. Initially, it provides an in-depth insight into exosome biogenesis characterization, laying groundwork for understanding their diverse intricate functions. Subsequently, explores regulatory roles various cells such neutrophils, macrophages, dendritic cells, T B cells. analysis elucidates how are thus contributing complexity pathophysiology. Additionally, this delves regulation metabolism subsequent dysfunction sepsis. It also establishes connection between coagulation cascade, which affects endothelial integrity promotes thrombogenesis Moreover, discusses dual progression resolution sepsis, exploring complex involvement inflammation healing Furthermore, underscores potential biomarkers therapeutic targets. Understanding mechanisms presents new opportunities novel interventions mitigate outcomes emphasizing promise research critical care settings.

Language: Английский

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The mammalian SKIV2L RNA exosome is essential for early B cell development

Science Immunology, Journal Year: 2022, Volume and Issue: 7(72)

Published: June 3, 2022

The SKIV2L RNA exosome is an evolutionarily conserved degradation complex in the eukaryotes. Mutations

Language: Английский

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DIS3: The Enigmatic Gene in Multiple Myeloma

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(4), P. 4079 - 4079

Published: Feb. 17, 2023

Recent studies have revealed the genetic aberrations involved in initiation and progression of various cancers, including multiple myeloma (MM), via next-generation sequencing analysis. Notably, DIS3 mutations been identified approximately 10% patients with MM. Moreover, deletions long arm chromosome 13, that includes DIS3, are present 40% Regardless high incidence deletions, their contribution to pathogenesis MM has not yet determined. Herein, we summarize molecular physiological functions focusing on hematopoiesis, discuss characteristics potential roles findings highlight essential RNA homeostasis normal hematopoiesis suggest reduced activity may be myelomagenesis by increasing genome instability.

Language: Английский

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SKI complex: A multifaceted cytoplasmic RNA exosome cofactor in mRNA metabolism with links to disease, developmental processes, and antiviral responses

Wiley Interdisciplinary Reviews - RNA, Journal Year: 2023, Volume and Issue: 14(6)

Published: June 29, 2023

RNA stability and quality control are integral parts of gene expression regulation. A key factor shaping eukaryotic transcriptomes, mainly via 3'-5' exoribonucleolytic trimming or degradation diverse transcripts in nuclear cytoplasmic compartments, is the exosome. Precise exosome targeting to various molecules requires strict collaboration with specialized auxiliary factors, which facilitate interactions its substrates. The predominant class targeted by protein-coding transcripts, carefully scrutinized for errors during translation. Normal, functional mRNAs turned over following protein synthesis Xrn1 5'-3'-exonuclease, acting concert Dcp1/2 decapping complex. In turn, aberrant eliminated dedicated surveillance pathways, triggered whenever ribosome translocation impaired. Cytoplasmic mRNA decay dependent on tight cooperation between evolutionary conserved co-factor-the SKI (superkiller) complex (SKIc). Here, we summarize recent findings from structural, biochemical, studies SKIc roles controlling metabolism, including links cellular processes. Mechanism action illuminated presentation spatial structure details ribosome. Furthermore, contribution usually converging recycling ribosomal subunits, delineated. crucial physiological role emphasized describing association dysfunction devastating human disease-a trichohepatoenteric syndrome (THES). Eventually, discuss functions regulation antiviral defense systems, cell signaling developmental transitions, emerging interdisciplinary investigations. This article categorized under: Turnover Surveillance > Turnover/Surveillance Mechanisms Regulation Stability Interactions Proteins Other Molecules RNA-Protein Complexes.

Language: Английский

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A Biallelic Variant of the RNA Exosome Gene, EXOSC4, Associated with Neurodevelopmental Defects Impairs RNA Exosome Function and Translation

Journal of Biological Chemistry, Journal Year: 2024, Volume and Issue: 300(8), P. 107571 - 107571

Published: July 14, 2024

The RNA exosome is an evolutionarily conserved complex required for both precise processing and decay. Pathogenic variants in EXOSC genes, which encode structural subunits of this complex, are linked to several autosomal recessive disorders. Here, we describe a missense allele the EXOSC4 gene that causes collection clinical features two affected siblings. This variant (NM_019037.3: exon3:c.560T>C) changes leucine residue within region proline (p.Leu187Pro). individuals show prenatal growth restriction, failure thrive, global developmental delay, intracerebral basal ganglia calcifications, kidney failure. Homozygosity damaging was identified by exome sequencing with Sanger confirm segregation. To explore functional consequences amino acid change, modeled EXOSC4-L187P corresponding budding yeast protein, Rrp41 (Rrp41-L187P). Cells express Rrp41-L187P as sole copy essential protein defects. Steady-state levels decreased compared controls, shows copurification other subunits. target transcripts accumulate rrp41-L187P cells, including 7S precursor 5.8S rRNA. Polysome profiles decrease actively translating ribosomes cells control incorporation pre-rRNA into polysomes. work adds have been human disease defines foundational molecular defects could contribute adverse phenotypes caused pathogenic variants.

Language: Английский

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In Situ, Fusion-Free, Multiplexed Detection of Small Extracellular Vesicle miRNAs for Cancer Diagnostics

Analytical Chemistry, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 19, 2024

Tumor-derived small extracellular vesicle (sEV) microRNAs (miRNAs) are emerging biomarkers for cancer diagnostics. Conventional sEV miRNA detection methods necessitate the lysis of sEVs, rendering them laborious and time-consuming potentially leading to damage or loss miRNAs. Membrane fusion-based

Language: Английский

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Harnessing endogenous transcription factors directly by small molecules for chemically induced pluripotency inception

Proceedings of the National Academy of Sciences, Journal Year: 2023, Volume and Issue: 120(21)

Published: May 16, 2023

Chemistry-alone approach has recently been applied for incepting pluripotency in somatic cells, representing a breakthrough biology. However, chemical reprogramming is hampered by low efficiency, and the underlying molecular mechanisms remain unclear. Particularly, compounds do not have specific DNA-recognition domains or transcription regulatory domains, then how small molecules work as driving force reinstating cells? Furthermore, to efficiently clear materials structures of an old cell prepare rebuilding new one? Here, we show that molecule CD3254 activates endogenous existing factor RXRα significantly promote mouse reprogramming. Mechanistically, CD3254–RXRα axis can directly activate all 11 RNA exosome component genes ( Exosc1–10 Dis3 ) at transcriptional level. Unexpectedly, rather than degrading mRNAs its substrates, mainly modulates degradation transposable element (TE)-associated RNAs, particularly MMVL30 , which identified barrier cell-fate determination. In turn, -mediated inflammation (IFN-γ TNF-α pathways) reduced, contributing promotion successful Collectively, our study provides conceptual advances translating environmental cues into inception, particularly, identifies CD3254–RXRα–RNA reprogramming, suggests modulation TE-mediated via CD3254-inducible important opportunities controlling fates regenerative medicine.

Language: Английский

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A comparison of size exclusion chromatography-based tandem strategies for plasma exosome enrichment and proteomic analysis

Analytical Methods, Journal Year: 2023, Volume and Issue: 15(45), P. 6245 - 6251

Published: Jan. 1, 2023

The capacities of four different size exclusion chromatography (SEC)-based methods were evaluated for the purpose establishing a “gold standard method” isolation exosomes from human plasma and thus accurate proteomic analysis.

Language: Английский

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Innate immune sensing of macromolecule homeostasis

Advances in immunology, Journal Year: 2024, Volume and Issue: unknown, P. 17 - 51

Published: Jan. 1, 2024

Language: Английский

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UPF1 plays critical roles in early B cell development

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: July 9, 2024

Abstract The ATP-dependent RNA helicase UPF1 plays a crucial role in various mRNA degradation pathways, most importantly nonsense-mediated decay (NMD). Here, we show that is upregulated during the early stages of B cell development and important for bone marrow. B-cell-specific Upf1 deletion mice severely impedes to late LPre-B transition, which V H -D J recombination occurs at Igh gene. Furthermore, indispensable recombination, without affecting D -J recombination. Intriguingly, genetic pre-arrangement gene rescues differentiation defect cells under deficient conditions. However, blocked again following Ig light chain leading failure into immature cells. Notably, interacts with regulates expression genes involved immune responses, cycle control, NMD, unfolded protein response Collectively, our findings underscore critical roles stage beyond, thus orchestrating development.

Language: Английский

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