Inhibition of U6 snRNA Transcription by PTEN | Science Publications

OnLine Journal of Biological Sciences

Stephanie Cabarcas¹  Laura Schramm¹  Kounosuke Watabe¹ 

关键词: RNA polymerase;    III transcription;    PTEN;    TFIIIB;    BRF2;   

DOI  :  10.3844/ojbsci.2010.114.125

学科分类：生物科学（综合）

来源: Science Publications

【 摘 要 】

Problem statement: RNA polymerase III (RNA pol III) is responsible for transcribingmany of the small structural RNA molecules involved in RNA processing and protein translation,thereby regulating the growth rate of a cell. RNA pol III transcribes both gene internal (tRNA) andgene external (U6 snRNA) promoters and proper initiation by RNA polymerase III requires thetranscription initiation factor TFIIIB. TFIIIB has been shown to be a target of repression by tumorsuppressors such as ARF, p53, RB and the RB-related pocket proteins. Also, TFIIIB activity isstimulated by the oncogenes c-Myc and the ERK mitogen-activated protein kinase. Recently, twoTFIIIB subunits, BRF1 and BRF2, have been demonstrated to behave as oncogenes, makingderegulation of TFIIIB activity and thus RNA pol III transcription an important step in tumordevelopment. PTEN is a commonly mutated tumor suppressor regulating cell growth, proliferation andsurvival. Thus, we sought to examine the potential role of PTEN in regulating U6 snRNAtranscription. Approach: We examined the potential for PTEN to regulate U6 snRNA transcriptionusing in vitro RNA pol III luciferase assays, western blotting and deletion analysis in cancer cell linesdiffering in their PTEN status. Results: Using breast, cervical, prostate and glioblastoma cancer cellswe demonstrate: (1) PTEN inhibition of gene external RNA pol III transcription is cell type specific,(2) PTEN-mediated inhibition of U6 transcription occurs via the C2 lipid-binding domain and (3)PTEN repression of U6 transcription occurs, at least in part, through the TFIIIB subunit BRF2.Conclusion/Recommendations: Our data demonstrates that regulation of the U6 snRNA gene byPTEN is mediated, in part by the TFIIIB oncogene BRF2, potentially identifying novel targets forchemotherapeutic drug design.

【 授权许可】

Unknown