EXOSC3 siRNA_Lentivectors
- Known as:
- EXOSC3 siRNA_Lentivectors
- Catalog number:
- i007148a
- Product Quantity:
- 500ng
- Category:
- -
- Supplier:
- ABM
- Gene target:
- EXOSC3 siRNA_Lentivectors
Related genes to: EXOSC3 siRNA_Lentivectors
- 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 siRNA_Lentivectors
Related articles to: EXOSC3 siRNA_Lentivectors
- 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 - Pathogenic variants in EXOSC3, a noncatalytic subunit of the RNA exosome, cause pontocerebellar hypoplasia type 1B (PCH1B), yet substantial variability in disease severity is observed among individuals carrying different EXOSC3 alleles. The molecular mechanisms of RNA exosome dysfunction in individuals carrying EXOSC3 p.G191 variants remains unresolved. To address this, we generated CRISPR/Cas9-engineered human cell models harboring EXOSC3 p.G191 variants and performed integrated transcriptomic, proteomic, and computational structural analyses. EXOSC3 p.G191 variants produced extensive, allele- and dosage-dependent alterations in gene expression and splicing, with heterozygous variants causing broad but attenuated disruption relative to homozygous EXOSC3 G191D/G191D cells. All EXOSC3 G191 variants promoted increased skipping of exon 3 in EXOSC3 transcripts, generating a short isoform predicted to encode an unstable proteoform. Molecular dynamics and λ-dynamics simulations predicted substantial thermodynamic destabilization of all EXOSC3 G191 variant proteoforms, consistent with reduced protein abundance and thermal stability measured by global proteomics and PISA. At the protein complex level, EXOSC3 p.G191 variants were associated with coordinated decreases in all RNA exosome core subunits and the exonuclease EXOSC10, consistent with destabilization of RNA exosome assembly and orphan protein decay. In contrast, the catalytic exonuclease DIS3 and multiple independent RNA processing pathways were upregulated, indicating compensatory recalibration of RNA metabolism. Together, these findings link variant-induced alternative splicing, RNA exosome complex destabilization, and adaptive network responses to phenotypic variability in EXOSC3 p.G191-associated disease. - Source: PubMed
Publication date: 2026/01/28
Wijeratne H R SagaraRunnebohm Avery MBarron Monica PHampton Ariana JLi RudongPeck Justice Sarah ALenceski Sophia HRooney James DSmith-Kinnaman Whitney RChang Gina SDoud Emma HKim JungsuPelletier StephaneLiu YunlongVilseck Jonah ZMosley Amber L