RNA polymerase III transcription, gene regulation, small noncoding RNA

RNA polymerase III (Pol III) transcribes genes encoding tRNA, 5S ribosomal RNA, and other classes of small noncoding RNA involved in translation and other critical processes. Pol III activity is a prerequisite for cell growth and is linked to nutrient availability and extracellular growth cues via oncogenic and tumor-suppressor signaling pathways. Aberrant activation of growth signaling factors can lead to elevated levels of Pol III transcription, a hallmark of cancer.

My lab uses genomic approaches to investigate Pol III transcription dynamics during differentiation and in response to extracellular cues and signaling events. We are particularly interested in understanding the regulatory mechanisms that promote or restrict Pol III activity and which underly Pol III dysregulation in cancer. Our recent work suggests that a specific Pol III subunit, POLR3G, which is highly expressed in proliferative cells and a myriad of cancer contexts, enhances Pol III transcription and drives expression of small NF90-associated (SNAR-A) noncoding RNA. We seek to better understand the mechanism of POLR3G-enhanced transcription, the function of SNAR-A and other Pol III-transcribed small RNA, and the role of POLR3G as a potential disease factor and future therapeutic target.