New Ribosome Modification Found in Colon Cancer

Researchers from the University of British Columbia identified a chemical modification on ribosomes that is lost in 45% of colorectal cancer patients, opening up new opportunities to treat the disease.

The ribosome is a complex molecule–made up of both RNA and protein–found in all living cells. It is the machinery that translates the genetic information from DNA into proteins, which carry out most functions of a cell. The reason that antibiotics are so effective against bacteria is because they inhibit ribosomes. 

“If you open a textbook, they will all say that ribosomes are assembled identically to one another, that there is no variation between ribosomes,” Artem Babaian, the lead scientist on the paper, said. “In the last three to four years that’s essentially been refuted.”

Evidence has come forward showing that the RNA component of ribosomes, or rRNA, can be chemically modified, and the modifications are variable between people.

When looking through sequencing data of the rRNA, Babaian noticed one chemical modification known as 1-methyl-3-α-amino-α-carboxyl-propyl pseudouridine was altered in colon cancer cells. This modification is found universally in all eukaryotes and has been conserved for a billion and a half years. 

 “This modification is supposed to be in 100% of ribosomal RNA molecules. So, every single ribosome in all eukaryotes should have it. It should never be absent,” Babaian said. But what he found was that colorectal cancer patients were losing this modification, which produced a new type of ribosome in cancer cells.

 “For me, one of the most important pieces of data in the paper is the evolutionary conservation”, Babaian said, “Something that has been with us since we were essentially a fungus, and cancer cells are losing that thing. It has to be doing something.”

 The team knocked out the protein that attaches the modification to the ribosome and saw an increase in the production of ribosomal proteins. The genes that were expressed in the knockout resembled the genes that are expressed in rapidly growing tumors.

 He says that once we uncover what this new type of ribosome is doing in cancer cells there are potential applications for new treatments.

 “We know that if we inhibit bacterial ribosomes we get antibiotics. Now the question is can we inhibit cancer ribosomes and create a new type of antibiotic.”