Laura Schramm

Differential Expression of the TFIIIB Subunits Brf1 and Brf2 in Cancer Cells

Stephanie Cabarcas, Joby Jacob, and Ingrid Veras, St. John’s University Students
Laura Schramm, Department of Biological Sciences, St. John’s College of Liberal Arts and Sciences

Abstract: RNA polymerase (pol) III transcription is specifically elevated in a variety of cancers and is a target of regulation by a variety of tumor suppressors and oncogenes.   Accurate initiation by RNA pol III is dependent on TFIIIB.  In higher eukaryotes, two forms of TFIIIB have been characterized.  TFIIIB required for proper initiation from gene internal RNA pol III promoters is comprised of TBP, Bdp1, and Brf1.  Proper initiation from gene external RNA pol III promoters requires TBP, Bdp1, and Brf2.  We hypothesized that deregulation of RNA polymerase III transcription in cancer may be a consequence of altered TFIIIB expression Here, we report: (1) the TFIIIB subunits Brf1 and Brf2 are differentially expressed in a variety of cancer cell lines: (2) the Brf1 and Brf2 promoters differ in activity in cancer cell lines, and (3) VAI transcription is universally elevated, as compared to U6, in breast, prostate and cervical cancer cells. We conclude that post-transcriptional regulation of the TFIIIB subunits Brf1 and Brf2 may be key molecular events dictating RNA pol III transcription rates in a breast, cervical and prostate cancer cell lines.