Transfer RNAs Play Role in Protein Synthesis Regulation

Researchers in Spain have demonstrated for the first time that transfer RNAs (tRNAs) for certain amino acids are altered at the epigenetic level in some types of cancer, and analysis of variants could provide information on tumor progression.

DNA dictates production of proteins, the buildings blocks of cells, by ribosomes. During this assembly line, tRNAs read the genetic information and provide the right amino acids to bind them. This universal mechanism serves all the proteins in the human body.  It was previously believed that these tRNAs repeated the same routine, couldn’t be regulated or modified, and didn’t play a relevant role in disease.  But Dr. Manel Esteller, Director of the Josep Carreras Leukaemia Research Institute, ICREA Research Professor and Genetics Chairman at the University of Barcelona, thought tRNAs warranted another look because of their variability.

"There are more than two hundred different transfer RNAs each attached to a specific amino acid. Such diversity in the human genome led us to think that they should be more than repetitive pieces, which were monotonously packing amino acids in boxes to make proteins, but they could also be individually regulated and contribute to the origin of certain pathologies,” Dr. Esteller says.

"There are more than two hundred different transfer RNAs each attached to a specific amino acid. Such diversity in the human genome led us to think that they should be more than repetitive pieces, which were monotonously packing amino acids in boxes to make proteins, but they could also be individually regulated and contribute to the origin of certain pathologies,” Dr. Esteller says.

First, bioinformatics tools were used to study expression patterns in human tumors. "We noticed that their expression profiles in cancerous tissues were different than in healthy parts, and they often depended on the affected organ," Dr. Esteller says. “[W]e went beyond computational data and demonstrated a couple of specific cases in the laboratory: a transfer RNA for the amino acid isoleucine ceased to be present in colon cancer, while in uterine cancer a switch was opened that activates the overexpression of a transfer RNA for the amino acid arginine.”

According to the results, the epigenetic lesion was associated with a worse clinical course in patients who had the tumor. When the team re-silenced this member of the protein assembly line, tumors stopped growing, always in preclinical studies. "Our work shows that these molecules are actively involved in the development of cancer and could be attractive targets for next-generation drugs," adds coauthor Dr. Margalida Rosselló-Tortella.

The work  was published recently in Molecular Cancer.