The structure of a ribosome seen from different angles overlaid on an image of liver cancer. Image credit: Mary McMahon (CC BY 4.0)
Ribosomes are cellular machines responsible for translating the genetic code into proteins. Research has shown that changes in ribosome activity can contribute to healthy cells becoming cancerous. Ribosomes consist of proteins and other molecules known as ribosomal RNAs (or rRNAs for short). Before they can become part of a ribosome, another type of molecule called snoRNAs must modify new rRNAs. Indeed, many of the modifications that allow rRNAs to accurately translate genetic information into proteins are introduced by snoRNAs. As such, it is possible that changes to snoRNAs could contribute to the creation of cancerous cells by affecting how ribosomes operate.
To explore this possibility, McMahon, Contreras et al. examined snoRNAs in healthy cells grown in the laboratory that have been given pro-cancer signals, in cancer from mice, and in samples from human cancer patients. The investigation revealed that the activation of growth signals – a hallmark of many cancers – affects the abundance of some snoRNAs and changes the pattern of rRNA modifications they make on ribosomes. Reducing the levels of one such snoRNA called SNORA24 led mice to develop fatty liver cancer when combined with cancer-promoting growth signals. Analyzing why reducing the levels of SNORA24 led to liver cancer, McMahon, Contreras et al. found that ribosomes lacking rRNA modifications introduced by SNORA24 made more mistakes when producing proteins coded for by certain genes.
These results contribute to the view of ribosomes as a key hub for the transformation of healthy cells into cancer cells. Increasing the error rate of ribosomes could be a key driver in further changes that drive cancer development. This study also highlights the role of snoRNAs in responding to growth signals, particularly in cancer. These findings identify snoRNAs as new potential diagnostic factors and treatment targets.
