Variable rRNA 2’- O -methylation fine-tunes ribosome function in Saccharomyces cerevisiae

Cellular processes are governed by the regulation of gene expression, often at the level of translation control. The mechanisms of control have been shown to operate at various levels, but there is growing evidence to suggest that rRNA modification patterns play a key role in driving translational modulation of the ribosome. We investigated the intricate relationship between modification status and the decoding activity of the ribosome. We found that the level of 2’- O -methylation at specific nucleotides in the rRNA affects the properties of the ribosome, with consequences for both Saccharomyces. cerevisiae cell growth and antibiotic sensitivity. More precisely, we demonstrate that methylations within the peptide exit tunnel play an important role in nascent peptide folding. We also demonstrate the modulation of IRES-driven translation by variable methylation at the intersubunit surface of the 60S ribosomal subunit. These findings deepen our understanding of the mechanisms by which 2’- O -methylation confers functional specificity on the ribosome.