Why should we care about tRNA modification?
Transfer RNA (tRNA) is at the heart of translation — the process at which the genetic code of an organism is deciphered into functional machines, i.e. proteins. In this process, the tRNA molecules work as adapters that proofread the code and, upon a successful match, add the correct amino acids, i.e. the building blocks that make up proteins. For this intricate process to function correctly, tRNA molecules need to be chemically modified at key positions of the molecule. This is achieved by specialized tRNA modification enzymes acting alone or as part of complex pathways. These chemical modifications provide structural integrity to the tRNA molecule and more importantly, they regulate the accuracy and speed of translation.
Despite their crucial role in a core function of life, we are only beginning to understand the vast implications of tRNA modification and the complexity of the underlying mechanisms. We know that in microorganisms, such as bacteria and yeast, tRNA modifications are seldom required when the growth conditions are optimal. However, once a cell with an aberrant tRNA modification profile encounters any form of stress, severe problems in translation, protein homeostasis, stress response pathways etc. start to emerge. As organismal complexity increases, so does the severity of the implications. For example, a fault in only one mitochondrial tRNA modifying enzyme gives rise to severe developmental disorders in humans, whereas problems in amino acid charging manifest as neurodegenerative diseases. Moreover, incorrect regulation of tRNA modification enzymes has been associated with breast cancer and various other forms of cancer.
The RNAcious laboratory studies the role of chemical tRNA modifications as modulators of translation, broadly exploring their impact on topics such as host-pathogen interaction, cancer formation and progression, and heterologous protein production.