Casein kinase 2 (CK2) is a bona fide member of the yeast SSU processome and links ribosome assembly to cell growth

Ribosome assembly is linked to growth. In both normal growth and development, but also in cancer, cells upregulate ribosome assembly in order to meet the protein synthesis needs of growing cells. However, the mechanism underlying the relationship between growth and ribosome assembly is poorly characterized. The Small Subunit Processome (SSUP) is a 6 MDa complex composed of ribosome assembly proteins, and the U3 snoRNA. It is responsible for the assembly and maturation of the small subunit of the ribosome. The CK2 kinase complex has been implicated in the regulation of cell growth and of all three RNA polymerases required for ribosome assembly. CK2 has been suggested to be part of the UtpC subcomplex of the SSUP by genome-wide affinity-purification/mass spec analyses. However, the membership of CK2 in the SSUP has not been validated by the standard criteria: (i) nucleolar localization, the site of ribosome biogenesis; (ii) association by co-IP with known SSUP proteins; and (iii) a ribosome assembly defect upon depletion of the candidate component. Here, we validate the membership of CK2 in the yeast SSUP. By literature curation, we show that the CK2 components are nucleolar. As well, all four CK2 subunits co-IP the SSUP protein Kre33. Lastly, depletion of both CKa1 and CKa2 catalytic subunits yields a synthetic lethal phenotype along with a statistically significant decrease (p-value [less than] 0.0001) in mature 18S and 25S rRNA. We thus propose that CK2 is a master regulator of ribosome assembly and may link growth to ribosome assembly in both development and in cancer.