Ask about this productRelated genes to: EXOSC3 antibody
- 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
Related articles to: EXOSC3 antibody
- The RNA exosome is an essential, evolutionarily conserved ribonuclease complex that processes and degrades many classes of RNA. The complex is composed of three structural 'cap' subunits (EXOSC1-3/Csl4, Rrp4, Rrp40; ), six structural 'core' subunits (EXOSC4-9/Rrp41,Rrp46,Mtr3,Rrp42,Rrp43,Rrp45), and a catalytic ribonuclease (DIS3 or DIS3L/Dis3). Cofactors that associate with the RNA exosome confer specificity to target specific RNAs for processing and/or decay. Missense mutations in genes encoding structural subunits of the RNA exosome have been linked to neurological diseases. Notably, several pathogenic mutations have been identified in that are associated with pontocerebellar hypoplasia type 1b (PCH1b). These pathogenic alleles cause a broad spectrum of clinical severity, suggesting variant-specific functional consequences. Given the high degree of conservation between the human and budding yeast RNA exosome complexes, we performed a systematic analysis of eight pathogenic EXOSC3 variants modeled in budding yeast Rrp40. We find that two Rrp40 variants cause growth defects, show distinct negative genetic interactions with RNA exosome cofactor mutants, and impair RNA processing in budding yeast. One of these variants, EXOSC3-Y109N/Rrp40-Y64N, had not been previously characterized in any mechanistic studies. Computational stability predictions and immunoblot analyses indicate that most EXOSC3/Rrp40 variants display reduced steady-state protein levels, but decreased protein levels do not strictly correlate with phenotype or disease severity, suggesting that individual variants disrupt RNA exosome function through distinct mechanisms. Collectively, our studies suggest that pathogenic EXOSC3 variants alter RNA exosome function through distinct mechanisms and provide insight into the specific molecular defects that could underlie pathology. - Source: PubMed
Publication date: 2026/08/02
Fasken Milo BLeung Sara WSerafim Leonardo FYan ChunliIntemann Madison LGable Dustin LBarañano Kristin WIvanov IvayloGhalei HomaCorbett Anita H - The RNA exosome plays a critical role in surveilling nuclear mRNA biogenesis and regulating co-translational mRNA decay in the cytoplasm. Unlike canonical translation, repeat-associated non-AUG (RAN) translation of a GGGGCC hexanucleotide repeat expansion (HRE) within an intron of the locus leads to the synthesis of neurotoxic dipeptide-repeat (DPR) proteins, contributing to the pathogenesis of frontotemporal dementia and amyotrophic lateral sclerosis (C9-ALS/FTD). However, it remains unclear whether aberrant RAN translation is monitored and regulated co-translationally or how HRE (C9-HRE) mRNA is degraded during this process. Here, we demonstrate that RAN translation triggers the rapid decay of C9-HRE mRNA. During this process, the RNA exosome engages the translating ribosome-C9-HRE mRNA complex to mediate RAN translation-coupled mRNA decay. Moreover, overexpression of EXOSC3, a key subunit of the RNA exosome cap, promotes RAN translation-coupled decay of C9-HRE mRNA and suppresses DPR production. In iPSC-derived neurons, a reduction in EXOSC3 levels blocks C9-HRE mRNA decay in a translation-dependent manner, further confirming its role in RAN translation surveillance. These findings highlight the essential function of the RNA exosome, particularly EXOSC3, in mitigating RAN translation-associated toxicity and preventing pathological DPR production. This work provides insights into potential therapeutic strategies for C9-ALS/FTD and may have broader implications for other disorders involving RAN translation. - Source: PubMed
Publication date: 2026/08/04
Wu YouLi LiTian JingLiu LeileiDu KunzhaoShao ZhichengCheng TianlinCao XinWang Tao - Thrombotic microangiopathy (TMA) is characterized by the classical triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. Complement inhibition with eculizumab is highly efficacious in TMA secondary to complement dysregulation. However, a growing number of eculizumab-nonresponsive TMAs are reported. Recently, a syndromic form of TMA due to recessive variants in RNA exosome components (EXOSC3 and EXOSC5) has been identified. The underlying pathogenesis remains unclear. - Source: PubMed
Publication date: 2026/07/22
Walsh Patrick RBasu UttiyaBarakat Tahsin StefanBeck Bodo BBertini EnricoBrocklebank VickyCorderio NunoĆomić JasminaAbazi-Emini NoraFluss JoelGeorge AnnetteBulow MarcusGibson BethHambleton SophieHoefele JuliaHunt DavidIvanov IvanJohnson SallyKotzaeridou UraniaLaštůvková JanaLunn AndrewMallett GracePappworth IsabelPhilippou HelenPlatzer KonradRobson JulieŠafka Brožková DanaSmith-Jackson KateSinha Manish DThompson GemmaWood KatrinaZanni GinevraProhászka ZoltánLaubova JanaAranka JuditBojtár ZsülietAntal-Konya ViolettaBologa CristinaKarava VasilikiKamilari ThessaliaGeorgiadou ElissavetTasic VeliborMarkova PetyaMarchbank Kevin JKavanagh David - (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