Genetic Interactions Show the Importance of rRNA Modification Machinery for the Role of Rps15p during Ribosome Biogenesis in S. cerevisiæ

Rps15p, an essential ribosomal protein, was previously shown to be critical for nuclear export of small subunit pre-particles. We have designed a synthetic lethal screen in Saccharomyces cerevisiae to identify its genetic partners and further elucidate its role during ribosomal biogenesis. Our screen revealed interactions with mutants affected at various stages during ribosome biogenesis, from early nucleolar steps to nuclear export. Mutations were identified in genes encoding proteins involved in early ribosome biogenesis steps, like the small subunit processome component Utp15p, the 90S pre-ribosome factor Slx9p and the H/ACA snoRNP core protein Nhp2p. In addition, we found a synthetic lethality with BUD23, a gene encoding a methyltransferase involved both in rRNA modification and small subunit nuclear export. Interestingly, deletion of snR36 or snR85, two H/ACA snoRNAs that direct modifications close to Rps15p's binding site on the rRNA, produces mild and opposite effects on growth in an rps15 hypomorphic background. These data uncover an unreported link between a ribosomal protein and rRNA modification machinery.