Studies in a budding yeast model suggest ribosomal defects as the molecular basis for PEHO syndrome

We show that missense mutations which model those found in PEHO syndrome cause a decrease in steady-state Hit1 protein levels and a significant reduction of box C/D snoRNA levels, defects in rRNA processing and altered translation fidelity. RiboMethSeq analysis of rRNAs isolated from actively translating ribosomes reveals site-specific changes in the rRNA modification pattern of PEHO syndrome yeast mutant cells. Our data suggest that PEHO syndrome is a ribosomopathy and reveal new aspects of the molecular basis of this disease in translation dysregulation.