The NuRD complex shapes RNA polymerase III activity at highly expressed tRNA gene clusters, tuning the dynamic range of cellular tRNA pools.

Abstract

RNA polymerase III (Pol III) transcription produces RNAs involved in core biological processes and is therefore coupled to fluctuating demands for protein synthesis and cell growth. However, the mechanisms underlying dynamic Pol III regulation remain incompletely understood. To address this gap, we investigated protein-protein interactions shared across multiple Pol III subunits to characterize the macromolecular interactome of Pol III, with special attention directed toward potential regulatory factors. Our survey uncovers interactions between Pol III and the NuRD (nucleosome remodeling and deacetylase) complex. We further show that NuRD localizes to active Pol III-transcribed genes, including tRNA gene clusters associated with notably high expression. Inhibiting NuRD-associated deacetylase activity increases Pol III transcription at these sites, suggesting that NuRD constrains Pol III activity and thereby modulates the dynamic range of Pol III-derived RNAs. These findings implicate NuRD as a chromatin-based mechanism linking signaling events and metabolic need with the dynamic availability of specific tRNA pools.