Abstract: Nep1 methylates the hypermodified psi1191 base of 18S rRNA and has an additional essential function during ribosome biogenesis. It is strongly conserved in eukaryotes and a point mutation causes the human Bowen-Conradi syndrome. To identify Deltanep1-specific genetic interactions, viable deletions were screened genome-wide (SGA). Due to its essential function, we used, for the first time, query strain (Deltanep1) with two additive suppressor conditions (mcRPS19B, nop6-1). Nep1 interacting genes correspond to ribosome biogenesis (RPS18A, RPS18B, RRP8, EFG1, UTP30), to ribosome quality control (UBP3, BRE5, UBP6) and to ribosome functional control (DOM34, no-go decay). Deletions in ribosome quality and functional control genes were synthetically sick with Deltanep1. They cope with malfunctions and the respective deletions strengthen the Deltanep1 growth deficiency. Except for Deltarps18b, deletions in the identified ribosome biogenesis genes were synthetically lethal with Deltanep1. While the synthetic lethalities of Deltarrp8 and Deltaefg1 may result from additive defects, the Deltautp30 deletion seems to be in close functional relationship. The Deltautp30 deletion itself has no phenotype but it enforced all nep1-1(ts) mutant phenotypes. Furthermore, its overexpression partially restored the nep1-1(ts) growth deficiency. Our genetic and biochemical data suggest that Utp30 and Nep1 act together during pre-ribosomal complex formation and, along with Rps18, provide the surface for the Rps19 assembly to the 90S pre-ribosome.CI - Copyright (c) 2012 John Wiley & Sons, Ltd.