THE DIM1 GENE RESPONSIBLE FOR THE CONSERVED M(2)(6)AM(2)(6)A DIMETHYLATION IN THE 3'-TERMINAL LOOP OF 18-S RIBOSOMAL-RNA IS ESSENTIAL IN YEAST

Biogenesis of cytoplasmic ribosomes universally involves methylation o f ribosomal RNA. Little genetic evidence is available about the functi onal role(s) of this conserved posttranscriptional modification. The o nly known methylase gene involved in rRNA maturation is ksgA in Escher ichia coli, which directs dimethylation of two adjacent; adenosines (m (2)(6)A(1518)m(2)(6)A(1519)) in the loop of a conserved hairpin near t he 3'-end of 16 S rRNA. This . tandem methylation is the only rRNA mod ification common to pre and eukaryotes. Disruption of ksgA confers res istance to the aminoglycoside antibiotic kasugamycin without significa ntly impairing viability. Here we report the cloning of the DIM1 gene encoding the homolog 18 S rRSA dimethylase in Saccharomyces cerevisiae . The yeast enzyme is evolutionary related to the ksgA protein. It car ries a distinctive lysine-rich-N-terminal extension with a potential p rotein kinase C phosphorylation site. Like ksgA, DIM1 belongs to the e rm family of prokaryotic 23 S rRNA dimethylases responsible for erythr omycin resistance. Surprisingly, disruption of DIM1 turns out to be le thal in yeast.