Researchers from Rockefeller University have discovered a compound in yeast that prevents the assembly of ribosomes, molecular machines that build proteins. Cells without ribosomes cannot divide, making the new compound a possible target for developing medications, including antifungal drugs. The findings are in a paper that was just published in the Cell journal.
Ribosomes act as protein factories and are necessary for the survival of the cell. They are composed of two subunits; one reads the genetic code and the other translates it into a protein by bonding the proper amino acids together. If a cell can’t build ribosomes, it can’t function or divide. While there are medications on the market that target ribosome activity, there aren’t any drugs that completely stop the assembly of new ribosomes.
The researcher team analyzed thousands of chemical compounds found in yeast cells. They utilized both genetic and chemical methods in their screening technique. The team discovered a previously unstudied compound called Rbin-1. The compound appeared to be targeting an enzyme that’s normally responsible for ribosome assembly. The research team isolated the targeted enzyme, Mdn1, to better study the effects. Through their research, the team confirmed that Rbin-1 selectively targets the Mdn1 enzyme, shutting down the assembly of ribosomes. This action prevents the growth and division of yeast cells without affecting other chemical processes.
The team’s findings provide new insights into ribosome assembly and the effects of inhibiting compounds such as Rbin-1. Rbin-1 is unique in that it stops cells from building ribosomes by targeting a single enzyme, Mdn1. The selectivity of Rbin-1 will allow scientists to learn more about ribosome assembly. The compound also has potential in the pharmaceuticals industry. Rbin-1 could be incorporated into antifungal medications and similar drugs. The development of new antifungal drugs has slowed down in recent years, making this discovery especially important.
Shigehiro A. Kawashima et al. Potent, Reversible, and Specific Chemical Inhibitors of Eukaryotic Ribosome Biogenesis. Cell (2016).