Inhibition of Gene External RNA Polymerase III Transcription by PTEN
Laura Schramm, Department of Biological Sciences, St. John’s College of Liberal Arts and Sciences
RNA polymerase III is responsible for transcribing many of the small structural RNA molecules involved in RNA processing and protein translation, thereby regulating the growth rate of a cell. Proper initiation by RNA polymerase III requires the transcription initiation factor TFIIIB. TFIIIB has been shown to be a target of repression by tumor suppressors such as ARF, p53, RB, and the RB-related pocket proteins. Also, TFIIIB activity is regulated by the oncogenes c-Myc and the ERK mitogen-activated protein kinase. PTEN is a commonly mutated tumor suppressor regulating cell growth, proliferation, and survival. Thus, we examined the potential for PTEN to regulate gene external RNA polymerase III transcription. Here, we report that PTEN inhibits both gene internal and external RNA polymerase III transcription in a variety of cervical, breast and prostate cancer cells. Deletion analysis suggests that the phosphatase domain is important in regulating gene internal RNA polymerase III transcription and the C2-lipid binding domain in PTEN is important in regulating gene external RNA polymerase III transcription, providing a novel mechanism by which PTEN regulates basal transcription. Additionally, we show that PTEN repression of gene external RNA polymerase III transcription occurs through TFIIIB.