Genes, composed of DNA, provide instructions for making RNA molecules and proteins. Activation of genes leads to transcription, a process in which DNA is copied into RNA with the help of enzymes called RNA polymerases. The research group of Fred van Leeuwen has investigated RNA polymerase III, the enzyme complex responsible for transcription of a class of genes called transfer-RNA (tRNA) genes. The tRNA molecules produced by tRNA genes play an essential role in the production of proteins. It is known that tRNA genes as a group are regulated based on the need of protein production, but how individual tRNA genes are regulated has remained a mystery in human cells as well as more simple organisms like budding yeast.
To identify novel regulators of tRNA gene transcription, the team used Epi-Decoder, a method recently developed by the Van Leeuwen group. Applying this in the model organism budding yeast, they examined which proteins in the cell are in close proximity to one of the tRNA genes.
In addition to known RNA Polymerase III components, they discovered the previously uncharacterized protein Ykr011c to be present at the tRNA gene. The authors renamed this protein Fpt1, an abbreviation for Factor in the Proteome of tDNAs number 1. Fpt1 specifically binds to tRNA genes, especially during stress conditions when their transcription needs to be repressed. Furthermore, Fpt1 discriminates between individual tRNA genes and shows a preference for strongly regulated tRNA genes. This evidence suggests that Fpt1 has tRNA gene-specific regulatory role. Indeed, deleting Fpt1 from the cell revealed that Fpt1 is a negative regulator of RNA polymerase III, the enzyme responsible for tRNA gene transcription.
Lead researcher Fred van Leeuwen says, "This discovery reminds us that even lesser-known proteins, like Fpt1, can be important in the world of gene regulation. Therefore, it is important to keep developing new unbiased methods to investigate DNA and the proteins that interact with it from different angles. Understanding the fundamental principles of gene regulation helps us to better understand the biology of the cell, and it might even teach us something about cancer in the future."