Project description:Analysis of the gene signature of steatosis associated to obesity in hepatocytes of Zucker fa/fa obese rats and their controls; identifying target genes linked to steatosis progression. or Obesity and insulin resistance-associated steatosis can be a non-inflammatory condition affecting hepatocytes or progress to steatohepatitis: a condition that can result in end-stage liver disease. Although molecular events leading to accumulation of lipid droplets in the liver have been identified individually, the complexity of the condition suggested that emergent target would be uncovered by a more comprehensive examination. Then, this study was aimed at establishing a gene signature of steatosis in hepatocytes and at identifying target genes linked to steatosis progression. Using Affymetrix oligonucleotide arrays, we compared transcriptomes of hepatocytes isolated from Zucker "fa/fa" obese rats with three different age-related grades of steatosis with those of their counterpart non-steatotic cells.
Project description:FA-SAT is a satellite DNA sequence present and transcribed in many Bilateria species, what may anticipate a conserved and significant function in these genomes. Here we prove that in cat and human cells, FA-SAT satellite transcripts play a nuclear function at the G1 phase of the cell cycle. We identified and demonstrated that the main FA-SAT non-coding RNA interactor is the PKM2 protein. Our work shows that the disruption of the FA-SAT ncRNA/PKM2 protein complex, by the depletion of either FA-SAT or PKM2, results in the same phenotype—apoptosis. Moreover, the ectopic overexpression of FA-SAT in tumour human cells did not affect the cell cycle progression. In sum, our data reveal a new player, FA-SAT RNA, a non-coding satellite RNA, which interacts with the PKM2 nuclear protein. This ribonucleoprotein is involved in apoptosis and cell cycle progression, what foresees a promising new target for studies in cancer processes that rely on these pathways.