Cell Growth Control by tRNase Ribotoxins from Bacteria and Yeast

Microbial endoribonuclease toxins (ribotoxins) ensure survival of their producers against other microbial competitors. Often, they cleave tRNA anticodons leading to tRNA depletion and cell death. The tRNases PrrC and zymocin from E. coil and dairy yeast Kluyveromyces lactis, respectively, attack tRNA anticodons that possess specific nucleobase modifications at their wobble position. Intriguingly, these modifications are similar and functionally conserved among prokaryotes and eukaryotes. Therefore, our idea was to take the basic biology of tRNase toxins and apply this to cell systems, including HeLa tumour cells, whose proliferation heavily relies on tRNA functioning for protein synthesis. Our pilot findings indicate that expression of the zymocin tRNase not only inhibits growth of the yeast Saccharomyces cerevisiae but also affects the viability of higher eukaryotic cells. Similarly, we observe that E. coil tRNase PrrC is lethal when expressed in yeast cells. Hence, microbial tRNase ribotoxins may be invoked as novel anti-proliferative factors for biomedical intervention schemes.