Diminished Activity of RNA Polymerase III Selectively Disrupts Tissues with the Most Actively Dividing Cells

The job of transcribing a cell’s nuclear genes is shared by three enzymes called RNA polymerases. Each is essential for life, and each transcribes a different set of genetic templates. Focusing on RNA polymerase III (Pol III), which is implicated in both heart disease and cancer, an exciting new paper by Yee et al. supports the growing conviction that Pol III might prove useful as a novel therapeutic target. Pol III is highly specialized to produce only short untranslated RNAs, such as the transfer RNAs (tRNAs), which convert genetic information into protein sequences. Pol III activity is tightly linked to cell proliferation, probably because of tRNA’s role in protein synthesis. To maintain a constant size over successive generations, cells must double their mass—consisting of 80%–90 % protein—before they divide. Ill-defined checkpoints ensure that adequate mass has