Genome-wide RNAi Screening Identifies Protein Modules Required for 40S Subunit Synthesis in Human Cells

• DOI: 10.1016/j.celrep.2015.11.061
• Publication Date: 2015-12-18T21:59:34Z
• Authors: Lukas Badertscher; Thomas Wild; Christian Montellese; Leila T. Alexander; Lukas Bammert; Marie Sarazova; Michael Stebler; Gabor Csucs; Thomas U. Mayer; Nicola Zamboni; Ivo Zemp; Peter Horvath; Ulrike Kutay
• Keywords: info:eu-repo/classification/ddc/570; Ribosomal Proteins; 0303 health sciences; QH301-705.5; Glutamine; Ubiquitin-Protein Ligases; Genomics; ribosome synthesis, RNAi screening, cullin E3 ubiquitin ligase, glutamine metabolism; 03 medical and health sciences; RNA, Ribosomal; RNAi screening; glutamine metabolism; Humans; RNA Interference; Biology (General); ribosome synthesis; cullin E3 ubiquitin ligase; ribosome synthesis; RNAi screening; cullin E3 ubiquitin ligase; glutamine metabolism; HeLa Cells

Ribosome biogenesis is a highly complex process requiring many assisting factors. Studies in yeast have yielded comprehensive knowledge of the cellular machinery involved this process. However, aspects ribosome synthesis are different higher eukaryotes, and global set mammalian factors remains unexplored. We used an imaging-based, genome-wide RNAi screen to find human proteins 40S ribosomal subunit biogenesis. Our analysis identified ∼300 factors, part essential protein modules such as small (SSU) processome, eIF3 chaperonin complexes, ubiquitin-proteasome system. demonstrate role for vertebrate-specific factor RBIS synthesis, uncover requirement CRL4 E3 ubiquitin ligase nucleolar biogenesis, reveal that intracellular glutamine supports production.