RNA polymerase III transcription and cancer: A tale of two RPC7 subunits.

ABSTRACT

RNA polymerase III composition is shaped by the mutually exclusive incorporation of two paralogous subunits, RPC7α and RPC7ß, encoded by genes POLR3G and POLR3GL in vertebrates. The expression of POLR3G and POLR3GL is spatiotemporally regulated during development, and multiple reports point to RPC7α-enhanced Pol III activity patterns, indicating that Pol III identity may underly dynamic Pol III transcription patterns observed in higher eukaryotes. In cancer, upregulation of POLR3G, but not POLR3GL, is associated with poor survival outcomes among patients, suggesting differences between RPC7α and RPC7ß further influence disease progression and may translate into future biomarkers and therapeutic strategies. Here, we outline our current understanding of Pol III identity and transcription and reexamine the distinct protein characteristics of Pol III subunits RPC7α and RPC7ß. Drawing on both structural and genomic studies, we discuss differences between RPC7α and RPC7ß and the potential mechanisms by which Pol III identity may establish differential activities during development and disease.