SRA

Emerging evidence suggests that changes in ribosomal RNA 2'O-ribose methylation (rRNA 2'OMe) in the human ribosome play a key role in regulating translation thereby contributing in setting particular phenotypes such as hallmarks of cancer cells. Here, by analysing the rRNA 2'OMe in a large series of 195 human primary breast tumours using the RiboMETH-seq approach we have identified the positions within the rRNA molecules which can tolerate the absence of 2'OMe in humans. The frequency of rRNA 2'OMe at some positions is highly stable between individuals (termed “stable”) whereas it can vary substantially at other positions (termed “variant”). Differential association of rRNA 2'OMe with breast cancer features, evolution and structure/function characteristics suggest the stable positions showing a low inter-variability might be required to maintain the core structure and thus the function of the ribosome – representing compulsory rRNA 2'OMe positions. In contrast, the variant positions displaying high inter-variability might be the source of regulatory events – representing plastic rRNA 2'OMe positions. Therefore our data issued from rRNA 2'OMe profiling of a large-scale human sample series bring the first compelling evidence to resolve two divergent long lasting visions of the role of rRNA 2'O-Me and sustain the emerging role of the ribosome plasticity in regulating translation in cancer. Overall design: rRNA 2'OMe profiling in a series of 195 primary breast tumours