A yeast nuclear fraction of unknown coin posit ion, named THIIIE, was reported previously to enhance transcription of tRNA and 5S rRNA genes in vitro. We show that TFIIIE activity Co-purifies with a specific subset of ribosomal proteins (RPs)which, as revealed by chromatin immunoprecipitation analysis, generally interact with tRNA and 5S rRNA genes, but not with a Pol II-specific promoter. Only Rp16Ap and Rp16Bp, among the tested RPs, were found associated to a TATA-containing tRNA (IIc)(TAT) gene. The RPL6A gene also emerged as a Strong multicopy suppressor of a conditional mutation in the basal transcription factor TFIIIC, while RPL26A and RoI 14A behaved as weak suppressors. The data delineate a novel extra-ribosomal role for one or a few RPs which, by influencing 5S rRNA and tRNA synthesis, Could play a key role in the coordinate regulation of (lie different sub-pathways required for ribosome biogenesis and functionality. (C) 2008 Elsevier Inc. All rights reserved.