The ribosomes, the ‘protein factories’ in our cells, can be altered by cancer genes, a new study from the University of Copenhagen shows. This has implications for our understanding of both normal development and diseases such as cancer.
In order for humans to develop and survive, our DNA holding the genetic code needs to be faithfully translated into proteins that perform most of the tasks within our cells. These proteins are produced by molecular factories called ribosomes and this protein production accounts for around 60 percent of all energy spent within a human cell.
“What we found was that ribosomes are not uniform engines that keep on spitting out proteins. Instead, they can be tuned and modified in different ways. It’s rather substantial, since it reveals to us how this fine tuning happens inside of the cell and adds an important piece to our understanding of basic and disease biology”, says Professor Anders Lund, director of Biotech Research and Innovation Centre (BRIC).
Since ribosomes and their protein production are involved in close to all biological processes, these new findings could be relevant for many diseases.
In their present study they took an infamous cancer gene called MYC, relevant for many cancers such as liver, prostate, breast and colorectal cancers, and expressed it in non-cancer cells and measured if the ribosomes were changed, which they were. They then created mutant cells to analyse the differences between cells containing ribosomes with and without a specific modification.
“We discovered that not only were the ribosomes differently modified, they also changed in functional terms so that they started producing different amounts of particular proteins. Our findings demonstrate that to promote cancer cell growth, the particular gene overexpressed in cancer induces changes on the ribosome that alters protein production. You could say that the cancer gene hijacks or modifies the protein factory” explains Martin Jansson, assistant professor at BRIC.
The relevance to human cancer was further demonstrated earlier this year in a study led by coauthor professor Henrik Nielsen, which demonstrated that the ribosome in a particular hematological cancer are also changed.
Potential drug targets
The researchers think that their findings could provide new treatment strategies for many different diseases.
“The fact that ribosomes change makes these ‘specialized ribosomes´ interesting as therapeutic drug targets. Since ribosomes translate all protein-coding genes that have a huge variety of cellular functions, using them as general drug targets may cause severe side effects. Now, that we know that ribosomes have altered sub-types, potentially linked to disease, we might design drugs that target only these specific sub-types. That is our hope, at least,” says Anders Lund.
The study has been published in the journal Nature Structural & Molecular Biology. Read the entire study “Regulation of translation by site-specific ribosomal RNA methylation”