RRP40 Antibody

Definition and Target Specificity

RRP40 antibodies are designed to recognize the EXOSC3 protein, a non-catalytic cap subunit of the RNA exosome complex. This complex possesses 3'→5' exoribonuclease activity and participates in RNA surveillance, processing, and turnover . RRP40 is evolutionarily conserved, with homologs identified in Saccharomyces cerevisiae (Rrp40), Drosophila melanogaster, and humans .

Key Features of RRP40 Antibodies

• Applications: Western blot (WB), ELISA, immunohistochemistry (IHC), immunoprecipitation (IP) .

• Reactivity: Species-specific variants available for humans, mice, rats, yeast, and Drosophila .

• Commercial Availability: 13 products across 6 suppliers, including monoclonal and polyclonal options .

Role in B Cell Antibody Diversification

RRP40 interacts with activation-induced cytidine deaminase (AID) to promote class-switch recombination (CSR) in B cells:

• Mechanism: RRP40 knockdown in CH12F3 B cells reduces CSR efficiency by 50–70% without affecting AID expression or transcription of target loci .

• Chromatin Recruitment: RRP40 associates with transcribed switch (S) regions in an AID-dependent manner, facilitating DNA deamination .

Neurodevelopmental Insights from Drosophila Models

Studies in Drosophila reveal RRP40’s essential role in neuronal development and homeostasis:

• Developmental Lethality: Global RRP40 depletion causes embryonic lethality, while neuronal-specific depletion leads to adult locomotor defects and reduced lifespan .

• Mushroom Body Defects: RRP40-deficient flies exhibit α-lobe thinning and β-lobe fusion in brain structures critical for learning and memory .

Cancer Diagnostics

A monoclonal RRP40 antibody (MMp40) demonstrates utility in distinguishing squamous cell carcinomas (SqCC) from adenocarcinomas (ADC):

Data sourced from immunohistochemical studies comparing MMp40 with p63 .

Functional Insights from Disease-Linked Mutations

Missense mutations in EXOSC3 (e.g., G11A, D87A) linked to pontocerebellar hypoplasia type 1B (PCH1B) alter RNA exosome function:

• Transcriptomic Dysregulation: RNA-seq of Drosophila RRP40 mutants reveals increased levels of non-coding RNAs (e.g., lncRNAs, snoRNAs) and synaptic regulators like Arc1, correlating with neuronal dysfunction .

• Rescue Experiments: Neuronal expression of human EXOSC3 restores climbing ability in mutant flies but fails to rescue viability, indicating developmental-stage-specific requirements .

Technical Considerations

• Cross-Reactivity: Some polyclonal RRP40 antibodies exhibit nonspecific staining in macrophages, whereas monoclonal variants (e.g., MMp40) show higher specificity .

• Validation: Knockdown/knockout models (e.g., rrp40Δ yeast) confirm antibody specificity for RNA exosome subunits .