Previous studies have shown that the ribosomal 5.8S rRNA of human cells is partially methylated in a tissue-specific fashion, a modification which occurs largely or entirely in the cytoplasm. More recent studies have shown that the 5.8S rRNA forms a covalent linkage with tumor suppressor p53 protein and have suggested that this RNA plays a functional role in protein elongation. We now show that the expression of p53 protein in Schizosaccharomyces pombe results in cells which: morphologically resemble transformed cells expressing mutant 5.8S rRNA; are equally compromised in their ability to sustain protein synthesis, in vitro; and contain polyribosome profiles which strongly resemble the elevated profiles which also are observed with mutated 5.8S rRNA. Taken together, these results provide new physiological evidence of the possibility that the 5.8S rRNA is an important target in the control of ribosome function during cell differentiation and oncogenesis.