EXOSC3 antibody - C-terminal region (ARP40230_P050)
- Known as:
- EXOSC3 (anti-) - C-terminal region (ARP40230_P050)
- Catalog number:
- arp40230_p050
- Product Quantity:
- USD
- Category:
- -
- Supplier:
- Aviva Systems Biology
- Gene target:
- EXOSC3 antibody - C-terminal region (ARP40230_P050)
Related genes to: EXOSC3 antibody - C-terminal region (ARP40230_P050)
- Gene:
- EXOSC3 NIH gene
- Name:
- exosome component 3
- Previous symbol:
- -
- Synonyms:
- hRrp40p, Rrp40p, RRP40, CGI-102, p10, hRrp-40
- Chromosome:
- 9p13.2
- Locus Type:
- gene with protein product
- Date approved:
- 2004-03-26
- Date modifiied:
- 2016-10-05
Related products to: EXOSC3 antibody - C-terminal region (ARP40230_P050)
Related articles to: EXOSC3 antibody - C-terminal region (ARP40230_P050)
- (1) Background: The characteristics of rare diseases (RDs) vary considerably-not only between different disease types but also between individual patients with the same condition. In the Roma community, we analyzed the most frequent rare genetic disorders related to the founder effect. (2) Methods: This retrospective study, conducted between January 2019 and January 2025 at the Clinical Genetics and Metabolics Outpatient Clinic in Košice, included 61 patients aged from infancy to 25 years diagnosed with hypomyelinating leukodystrophy 14, pontocerebellar hypoplasia type 1B, neuronal ceroid lipofuscinosis 7, or TMEM70 deficiency. (3) Results: This study includes the largest known cohort of patients with hypomyelinating leukodystrophy 14 caused by the c.-273_-271delTCA mutation, predominantly affecting males ( = 17). The disorder is severe, with most patients dying before one year of age, and is characterized by inspiratory stridor, axial hypotonia, spastic quadriparesis, pseudobulbar signs, and microcephaly. In a separate group with pontocerebellar hypoplasia type 1B, six Roma patients (three males, three females) shared the same mutation. Diagnosis occurred at an average age of 8.8 months, and most children did not survive beyond three years. Common features included microcephaly, severe hypotonia, and spastic quadriplegia. Thirteen children from eight families were diagnosed with neuronal ceroid lipofuscinosis 7, all carrying the same mutation. Symptoms typically began with psychomotor regression between ages 3 and 4, along with intellectual disability and seizures, which were more frequent in males. The mean age at diagnosis was 4.5 years, and eight children died before age nine. Finally, 25 patients with TMEM70 deficiency associated with Roma ancestry were identified, predominantly females, with a mean age of 9.95 years and the oldest patient aged 25. Four children died due to severe metabolic crises. Common findings included intellectual disability, global hypotonia, hypertrophic cardiomyopathy, epilepsy, and failure to thrive. (4) Conclusions: Most rare diseases are genetic and carry high morbidity and mortality, with no targeted therapies currently available. Their increased prevalence in the Roma population reflects founder effects and high consanguinity. Prenatal and newborn screening, along with voluntary carrier testing for couples, is essential for proactive health management. - Source: PubMed
Publication date: 2026/04/29
Drobňaková SimonaAndrejková MáriaŠaligová JanaPotočňáková ĽudmilaVargová VeronikaKuchta MilanBeňačka RomanBarkai László - The RNA exosome complex (EXOSC1-10) orchestrates 3-5 RNA processing and decay, yet its family-wide landscape and clinical relevance in lung adenocarcinoma (LUAD) remain incompletely defined. Here, we conducted an integrative multi-omics analysis of EXOSC family members in LUAD using public transcriptomic and proteomic resources, external validation cohorts, and single-cell data. Across TCGA (59 normal vs. 515 tumors), all EXOSC genes were significantly upregulated in tumors, with concordant increases for most proteins in CPTAC and immunohistochemistry evidence from the Human Protein Atlas. Survival analyses identified EXOSC2, EXOSC3 and EXOSC5 as prognostically informative, with elevated EXOSC2/EXOSC5 also associated with inferior disease-specific survival. Receiver operating characteristic analyses indicated moderate-to-high diagnostic performance for several EXOSC genes, supported by qRT-PCR validation in LUAD cell lines and confirmation in GSE31210. Clinicopathological correlations linked EXOSC1-5 and EXOSC8-10 to advanced stage and metastatic features, whereas EXOSC6 and EXOSC7 showed comparatively limited or context-dependent associations, suggesting functional heterogeneity within the family. Genomic profiling revealed recurrent alterations in 11.83% of patients, with EXOSC4 exhibiting the highest alteration frequency (predominantly amplifications), and network analyses identified core interacting partners centered on RNA surveillance machinery. EXOSC expression was broadly correlated with RNA modification regulators (mA/mC/mA) and displayed heterogeneous relationships with immune checkpoint genes and immune infiltration, while higher EXOSC expression consistently associated with lower ESTIMATE-derived microenvironment scores and an immune profile characterized by Th2/T helper enrichment with reduced cytotoxic and antigen-presenting populations. Gene set enrichment analyses implicated cell-cycle regulation, senescence, chromatin-related programs and extracellular matrix pathways, and EXOSC-high tumors were associated with increased tumor mutational burden and homologous recombination deficiency, together with enrichment of DNA damage response pathways. Single-cell analysis (GSE146100) localized highest EXOSC expression to proliferating monocytes/macrophages and suggested TGF-β-linked communication with endothelial and T-cell compartments. Exploratory translational analyses further indicated an association between EXOSC9 and predicted cisplatin sensitivity. Collectively, these findings position the EXOSC family as a clinically and biologically relevant axis in LUAD, linking RNA surveillance dysregulation to immune contexture and genomic instability, and highlight subunit-specific heterogeneity that warrants mechanistic validation. - Source: PubMed
Publication date: 2026/05/22
Li NingWang XiaoleiChu TingtingPan YongxinZhang Xuezhong - Defects in RNA metabolism are a defining feature of neurodevelopmental disease, yet how RNA decay pathways contribute to human brain development remains poorly understood. Mutations in ubiquitously expressed RNA surveillance factors often cause highly tissue-selective disease, highlighting a central paradox in human biology. The RNA exosome is a conserved ribonuclease complex traditionally viewed as a housekeeping machine for RNA turnover, yet recessive mutations in genes encoding structural subunits of the complex disproportionately cause neurological disease, suggesting an instructive role in nervous system development. Here, we show that the RNA exosome regulates the temporal progression of gene expression programs during human cerebellar differentiation. Using CRISPR-engineered human cerebellar organoids modeling EXOSC3 variants, we find that RNA exosome dysfunction does not broadly alter transcript abundance, but instead disrupts transitions between developmental states. Mutant organoids exhibit incomplete and mis-timed resolution of early transcriptional programs, altered lineage specificity, and impaired coordination of maturation-associated gene expression programs, with pronounced effects in neuronal lineages, particularly Purkinje cells and rhombic lip-derivatives. These defects are accompanied by disorganized laminar architecture and reduced coordination of neuronal activity, despite preserved intrinsic excitability. Together, our findings establish RNA surveillance as a key regulator of developmental timing, lineage fidelity, and neurodevelopmental disease. - Source: PubMed
Publication date: 2026/04/30
Barr Nina ABaltov BozhidarKang Rylee EGada Jash JWade Matthew JTjoa Ethan NLee VivianSeth AnoothiDzirasa KafuiSchaffer Ashleigh EKim HyunminMorton Derrick J - The adenosine deaminase acting on RNA (ADAR) enzymes deaminate adenosine to inosine in double-stranded (ds)RNA. Mammals express two catalytically active enzymes: ADAR1, which is ubiquitously expressed and essential for innate immune homeostasis, and ADAR2, which is enriched in the brain and vascular system. Here, we investigate the ADAR2 interactome and uncover a shared interaction network with ADAR1, including multiple components of the RNA exosome complex, a multi-subunit RNase involved in RNA processing, turnover, and surveillance. The interactions between ADARs and RNA exosome components are nuclear, and resistance to RNase A treatment implies their close proximity. We validated these interactions by immunoprecipitation of both endogenous and epitope-tagged ADAR proteins in multiple cell lines and mapped the interaction interfaces to their dsRNA-binding domains. Exploiting an MS2-MCP tethering system, we show that recruitment of ADAR1 or ADAR2 to the 3' UTR of a reporter transcript decreases its stability. This decrease in RNA levels was reversed when EXOSC3 was depleted, demonstrating that this destabilizing effect of ADARs on RNA is via the RNA exosome complex. Finally, knockdown of ADARs perturbs rRNA processing, a canonical function of the nuclear exosome, demonstrating a cellular consequence of disrupting ADAR-exosome interactions. - Source: PubMed
Vukić DraganaDu QiupeiCherian AnnaAmoruso DamianoBrožinová KvětoslavaWacheul LudivineLacovich ValentinaZorbas ChristianeYadav LeenaSedmík JiříKeskitalo SallaHajji KhadijaStejskal StanislavVarjosalo MarkkuLafontaine Denis L JKeegan Liam PO'Connell Mary A - Pontocerebellar hypoplasia (PCH) comprises a group of rare neurodevelopmental disorders characterized by prenatal-onset cerebellar and pontine atrophy, often leading to severe motor and cognitive impairments. While advances in genetic diagnostics have improved our understanding, the full spectrum of causative mutations remains unclear, particularly in underrepresented populations. This study aims to delineate the clinical and genetic characteristics of Iranian patients with PCH. We conducted comprehensive clinical evaluations, brain imaging, and laboratory tests, followed by whole-exome sequencing (WES) in Iranian patients with PCH to establish genotype-phenotype correlations. In silico structural and modeling analyses were performed to assess the impact of novel variants on protein function. Ten unrelated patients were diagnosed with different PCH subtypes. Microcephaly and spasticity were observed in 80% of cases, while hypotonia, psychomotor retardation, and speech problems were present in all patients. Additional features included nystagmus (40%), ataxia (20%), decreased deep tendon reflexes (50%), respiratory insufficiency (10%), feeding difficulties (30%), scoliosis (10%), cognitive deficits (20%), seizures (40%), and vision problems (10%). Genetic analysis identified eight pathogenic variants, including four reported mutations in RARS2, EXOSC3, and TSEN54, and four novel mutations in SEPSECS, and RARS2. A recurrent missense variant (EXOSC3: c.395 A > C) was detected in 40% of cases. This study expands the mutational spectrum of PCH by identifying novel variants and underscores the disorder's genetic heterogeneity. The clinical manifestations ranged from mild developmental delay to severe neurodevelopmental decline with respiratory insufficiency and seizures. Our findings provide valuable insights into genotype-phenotype correlations, facilitating early diagnosis and personalized management strategies. Additionally, these results contribute to genetic counseling and future functional studies to elucidate disease mechanisms. - Source: PubMed
Publication date: 2026/03/11
Rezaei ZahraEmami FarnooshHeidari MortezaMohammadi MahmoudYousefian MiladBadv Reza ShervinKowkabi SafouraMahdieh NejatAshrafi Mahmoud Reza