A chromatin-associated regulator of RNA Polymerase III assembly at tRNA genes revealed by locus-specific proteomics

Maria Elize van Breugel; Ila van Kruijsbergen; Chitvan Mittal; Cor Lieftink; Ineke Brouwer; Teun van den Brand; Roelof J.C. Kluin; Liesbeth Hoekman; Renée X. de Menezes; Tibor van Welsem; Andrea Del Cortona; Muddassir Malik; Roderick L. Beijersbergen; Tineke Laura Lenstra; Kevin J. Verstrepen; B. Franklin Pugh; Fred van Leeuwen

doi:10.1016/j.molcel.2023.10.037

Molecular BiologyMolecular CellNov 22, 2023

Peer-reviewed journal article

A chromatin-associated regulator of RNA Polymerase III assembly at tRNA genes revealed by locus-specific proteomics

Maria Elize van Breugel iD, Ila van Kruijsbergen, Chitvan Mittal, Cor Lieftink iD, Ineke Brouwer iD, Teun van den Brand iD, Roelof J.C. Kluin iD, Liesbeth Hoekman iD, Renée X. de Menezes iD, Tibor van Welsem, Andrea Del Cortona iD, Muddassir Malik iD, Roderick L. Beijersbergen iD, Tineke Laura Lenstra iD, Kevin J. Verstrepen iD, B. Franklin Pugh iD, Fred van Leeuwen iD

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Abstract

Transcription of tRNA genes by RNA Polymerase III (RNAPIII) is tightly regulated by signaling cascades in response to nutrient availability. The emerging notion of differential tRNA gene regulation implies the existence of additional regulatory mechanisms. However, tRNA gene-specific regulatory factors have not been described. For that reason, we decoded the proteome of a single native tRNA gene locus in yeast. We observed dynamic reprogramming of the core RNAPIII transcription machinery upon nutrient perturbation. In addition, we identified Fpt1, a protein of unknown function. Fpt1 uniquely occupied tRNA genes but its occupancy varied and correlated with the efficiency of RNAPIII eviction upon nutrient perturbation. Decoding the proteome of a tRNA gene in the absence of Fpt1 revealed that Fpt1 promotes eviction of RNAPIII. Cells without Fpt1 also showed impaired shutdown of ribosome biogenesis genes upon nutrient perturbation. Our findings provide support for a chromatin-associated mechanism required for RNAPIII eviction from tRNA genes and for tuning an integrated physiological response to changing metabolic demands. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=118 SRC="FIGDIR/small/534528v1_ufig1.gif" ALT="Figure 1"> View larger version (34K): org.highwire.dtl.DTLVardef@1b2ef53org.highwire.dtl.DTLVardef@7e6234org.highwire.dtl.DTLVardef@1614b5borg.highwire.dtl.DTLVardef@9a4933_HPS_FORMAT_FIGEXP M_FIG C_FIG