Gender Specific Differences in RNA Polymerase III Transcription.

Abstract

RNA polymerase (pol) III transcribes a variety of untranslated RNAs responsible for regulating cellular growth and is deregulated in a variety of cancers. In this study, we examined gender differences in RNA pol III transcription in vitro and in vivo. Expression levels of U6 snRNA, tMet, and known modulators of RNA pol III transcription were assayed in male and female derived adenocarcinoma (AC) lung cancer cell lines and male and female C57BL/6J mice using real time quantitative PCR. Methylation status of the U6 snRNA promoter was determined for lung and liver tissue isolated from male and female C57BL/6J mice by digesting genomic DNA with methylation sensitive restriction enzymes and digestion profiles were analyzed by qPCR using primers spanning the U6 promoter. Here, we demonstrate that RNA pol III transcription is differentially regulated by EGCG in male and female derived AC lung cancer cell lines. Basal RNA pol III transcript levels are significantly different in male and female derived AC lung cancer cell lines. These data prompted an investigation of gender specific differences in RNA pol III transcription in vivo in lung and liver tissue. Herein, we report that U6 snRNA RNA pol III transcription is significantly stimulated in the liver tissue of male C57BL/6J mice. Further, the increase in U6 transcription correlates with a significant inhibition in the expression of p53, a negative regulator of RNA pol III transcription, and demethylation of the U6 promoter in the liver tissue of male C57BL/6J mice. To the best of our knowledge, this is the first study demonstrating gender specific differences in RNA pol III transcription both in vivo and in vitro and further highlights the need to include both male and female cell lines and animals in experimental design.