Molecular Cell n

gBiogenesis of eukaryotic ribosomes is a highly coordinated process that largely takes place in the nucleolus. Work by many groups has defined the processing pathway for ribosomal RNA (rRNA) and identified 170 proteins involved in ribosome biogenesis, while proteomic analyses have provided a roughly outlined pathway of preribosome assembly in Saccharomyces cerevisiae (Fatica and Tollervey, 2002; Venema and Tollervey, 1999). Three of the four rRNAs (18S, 5.8S, and 25/28S rRNA) are derived from the 35S rRNA precursor transcribed by RNA polymerase I, while the fourth rRNA (5S rRNA) is transcribed separately by RNA polymerase III. The 35S pre-rRNA is packaged into a 90S ribonucleoprotein particle (RNP) together with a subset of assembly factors and ribosomal proteins (r-proteins). After undergoing extensive site-specific modifica-tions, internal and external spacer regions (ITS and ETS) ar