AUTHOR=Cheng Ruiying , Van Bortle Kevin 

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

JOURNAL=Frontiers in Molecular Biosciences

VOLUME=9

YEAR=2023

URL=https://www.frontiersin.org/journals/molecular-biosciences/articles/10.3389/fmolb.2022.1073795

DOI=10.3389/fmolb.2022.1073795

ISSN=2296-889X

ABSTRACT=<p>RNA polymerase III composition is shaped by the mutually exclusive incorporation of two paralogous subunits, RPC7α and RPC7β, encoded by genes <italic>POLR3G</italic> and <italic>POLR3GL</italic> in vertebrates. The expression of <italic>POLR3G</italic> and <italic>POLR3GL</italic> 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 <italic>POLR3G</italic>, but not <italic>POLR3GL</italic>, is associated with poor survival outcomes among patients, suggesting differences between RPC7α and RPC7β 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 RPC7β. Drawing on both structural and genomic studies, we discuss differences between RPC7α and RPC7β and the potential mechanisms by which Pol III identity may establish differential activities during development and disease.</p>