Ribosomal RNA methylation induced by MYC regulates translation

Abstract Ribosomes are complex ribozymes that interpret genetic information by translating messenger RNA (mRNA) into proteins. Natural variation in ribosome composition has been documented in several organisms, and can stem from several different sources. A key question is whether specific control over ribosome heterogeneity represents a mechanism by which translation can be regulated. We used RiboMeth-seq to demonstrate that differential 2’-O-methylation of ribosomal RNA (rRNA) represents a considerable source of ribosome heterogeneity in human cells, and that modification levels at distinct sites can change dynamically in response to upstream signalling pathways. Ablation of one prominent methylation, induced by MYC oncogene expression, resulted in altered translation of select mRNAs and corresponding changes in cellular phenotypes. Thus, differential rRNA 2’-O-methylation can give rise to ribosomes with specialized function. This constitutes a broader mechanism where the specific regulation of rRNA modification patterns fine-tune translation.