Ask about this productRelated genes to: EXOSC3 Blocking Peptide
- 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 Blocking Peptide
Related articles to: EXOSC3 Blocking Peptide
- 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 - Reproductive traits related to litter size are the main indicators of reproductive efficiency in pig production and are continuously evaluated for the selection of maternal lines. Several environmental and genetic factors are involved with the development of these traits. Genome-wide association studies (GWAS) allow a better understanding of the genetic control of complex traits, especially those with low heritability (h). Therefore, this study aims to estimate the genetic parameters and to identify genomic regions and candidate genes associated with total number born (TNB), number born alive (NBA), and viable piglets at Day 5 (PV5) in a Large White female line. For this, 17,011 phenotypic records, 190,000 pedigree records, and 4366 animals genotyped with the Illumina 50 K and 80 K panels were used. Estimates of h, genetic (r) and phenotypic (r) correlations, and GWAS were performed with the BLUPF90 family programs. Positional candidate genes, their main biological processes, and networks were investigated using the Ensembl database and the BioMart, PANTHERdb, and STRING tools. The studied traits presented low h estimates, but with high and positive r and r. In the GWAS, 14 significant genomic windows were identified for TNB, 10 for NBA, and 15 for PV5. These regions include 157 genes for TNB, 101 for NBA, and 140 for PV5, mapped across 10 different chromosomes. Among the genes located in those regions, the ESR1, THRB, SLIT2, and ZBTB2 were common to the three traits and are involved in processes of hormonal regulation, embryogenesis, immunity, and homeostasis. Moreover, 12 of those genes were new positional candidates for TNB, NBA, or PV5. Among them, we highlight the FSTL4, PAPPA, and TCF7 genes associated with PV5, which are involved with hormonal regulation, growth factors, and immunity, respectively. The SLIT2, MTHFD1L, OVOL2, SHB, and EXOSC3 genes, involved with embryogenesis and neurogenesis, were associated with TNB and NBA. Furthermore, uncharacterized genes, such as ENSSSCG00000058091, related to mitochondrial homeostasis, were associated with TNB, while ENSSSCG00000040472, related to protein synthesis, was identified for PV5. These new findings reveal common and exclusive genetic mechanisms that may influence important litter traits in pigs, helping the development of breeding strategies to optimise reproductive efficiency. - Source: PubMed
Publication date: 2026/02/12
Oselame GuilhermePadilha Suelen FernandesCantão Maurício EgídioPeixoto Jane de OliveiraZampar AlineIbelli Adriana Mércia GuaratiniCarreño Luis Orlando DuitamaLopes Jader SilvaFreitas Pedro Henrique FerreiraFreitas Marcelo SilvaLedur Mônica Corrêa