Traffic Jam in the Protein Factory

When genes are being read too slowly, a cell is threatened by burnout
Dr. Sebastian Leidel and Dr. Danny Nedialkova
© MPI Münster / J. Müller-Keuker

The production of proteins in cells is an absolutely essential process: difficulties that may arise in the protein factory will have a strong impact on the whole organism - diseases are often the result. Max Planck Research group leader Dr. Sebastian Leidel and his colleague Dr. Danny Nedialkova have now for the first time in living cells shown that a tiny missing modification on transfer-RNA (tRNA) is slowing down the protein production and causes a traffic jam in the protein factory. The consequence: protein chains are misfolded. Protein aggregates, as we know them from Alzheimer and Parkinson, will accumulate. The cells try to repair the damage, however, they do not always succeed and finally collapse. This study, published in the renowned scientific journal Cell on June 4th, 2015, provides a first direct explanation of how tiny defective or missing modifications on tRNA could elicit neurodegenerative diseases.

Publication

Nedialkova D, Leidel S. Optimization of codon translation rates via tRNA modifications maintains proteome integrity. Cell 2015: epub.

Yeast cells without modified tRNA are vulnerable to stress. Yeast cells on a agar plate in presence of a chemical stressor. Mutant cells that miss an enzyme for the modification of tRNA (rows 2 & 3) clearly grow slower than normal cells (row 1).
© MPI Münster / Danny Nedialkova