The perinucleolar compartment (PNC) forms in cancer cells and is highly enriched with a subset of polymerase III RNAs and RNA-binding proteins. Here we report that PNC components mitochondrial RNA-processing (MRP) RNA, pyrimidine tract-binding protein (PTB), and CUG-binding protein (CUGBP) interact in vivo, as demonstrated by coimmunoprecipitation and RNA pull-down experiments. Glycerol gradient analyses show that this complex is large and sediments at a different fraction from known MRP RNA-containing complexes, the MRP ribonucleoprotein ribozyme and human telomerase reverse transcriptase.
View Article and Find Full Text PDFThe pregnane X receptor (PXR; NR1I2) and the farnesoid X receptor (FXR; NR1H4) regulate the expression of many major metabolic enzymes. With the pig being used as a model for humans in metabolic and toxicological studies and also an important food animal, we characterized the transactivation profile of the porcine orthologs of these receptors, pgPXR and pgFXR. We compared the transactivation profiles of these receptors and their splice variants to their human orthologs using mostly endogenous ligands.
View Article and Find Full Text PDFThe perinucleolar compartment (PNC) is a subnuclear body characterized by its location to the periphery of the nucleolus. The PNC is a dynamic structure and is highly enriched in RNA-binding proteins and pol III RNA. The structural stability of the PNC is dependent on continuous pol III transcription and the presence of key proteins.
View Article and Find Full Text PDFThe perinucleolar compartment (PNC) is a distinct nuclear body that localizes to the nucleolar periphery. The PNC is predominantly found in cancer cells, and recent evidence suggests that PNC prevalence can be a pan-cancer marker for tumors of solid tissue origin. The PNC is a heritable structure enriched with newly transcribed pol III RNAs and RNA-binding proteins, which exchange rapidly with the surrounding nucleoplasm.
View Article and Find Full Text PDFBackground: The perinucleolar compartment (PNC) is a subnuclear structure localized at the nucleolar periphery. Previous studies using breast cancer as a model system demonstrated that PNC prevalence (the percentage of cells with 1 or more PNC) increased with disease progression and was associated with poor patient outcomes.
Methods: To evaluate the validity of developing PNC prevalence as a novel pancancer prognostic marker, the authors investigated whether PNC prevalence was correlated with malignancy in a spectrum of tissue types and evaluated its selective association with malignancy under various experimental conditions.
Ataxia-Telangiectasia (A-T) is a genetic disorder causing cerebellar degeneration, immune deficiency, cancer predisposition, chromosomal instability and radiation sensitivity. Among the mutations responsible for A-T, 85% represent truncating mutations that result in the production of shorter, highly unstable forms of ATM (AT-mutated) protein leading to a null ATM phenotype. Several ATM-deficient mice have been created however none reflects the extent of neurological degeneration observed in humans.
View Article and Find Full Text PDFThe pregnane X receptor (PXR) plays a crucial role in xenobiotic and drug metabolism, being the major transcriptional regulator of cytochrome P-450 monooxygenase 3A4, which metabolizes more than 50% of all clinically used drugs. Recent pharmacodynamic studies have shown that the mouse is not an ideal model for predicting human clinical drug study outcomes. Therefore, we characterized the porcine PXR (pPXR) gene to evaluate the utility of the pig as an alternate preclinical animal model.
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