Yeast proteins related to the p40/laminin receptor precursor are required for 20S ribosomal RNA processing and the maturation of 40S ribosomal subunits

Numerous studies have linked the overexpression of the M-r 37,000 laminin r eceptor precursor (37-LRP) to tumor cell growth and proliferation, The role of this protein in carcinogenesis is generally considered in the context o f its putative role as a precursor for the M-r 67,000 high-affinity laminin receptor. Recent studies have shown that 37-LRP, also termed p40, is a com ponent of the small ribosomal subunit indicating that it may be a multifunc tional protein. The p40/37-LRP protein is highly conserved phylogenetically , and closely related proteins have been identified in species as evolution arily distant as humans and the yeast, Saccharomyces cerevisiae. Yeast homo logues of p40/37-LRP are encoded by a duplicated pair of genes, RPS0A and R PS0B, The Rps0 proteins are essential components of the JOS ribosomal subun it, Previous results have shown that cells disrupted in either of the RfS0 genes have a reduction in growth rate and reduced amounts of 40S ribosomal subunits relative to wild-type cells, Here, we show that the Rps0 proteins are required for the processing of the 20S rRNA-precursor to mature 18S rRN A, a late step in the maturation of 40S ribosomal subunits, Immature subuni ts that are depleted of Rps0 protein that contain the 20S rRNA precursor ar e preferentially excluded from polysomes, which indicates that their activi ty in protein synthesis is dramatically reduced relative to mature JOS ribo somal subunits, These data demonstrate that the assembly of Rps0 proteins i nto immature 40S subunits and the subsequent processing of 20S rRNA represe nt critical steps in defining the translational capacity of yeast cells. If the function of these yeast proteins is representative of other members of the p40/37-LRP family of proteins, then the role of these proteins as key components of the protein synthetic machinery should also be considered as a basis for the linkage between the their overexpression and tumor cell gro wth and proliferation.