Traffic jam in the protein factory

When genes are being read too slowly, a cell is threatened by burnout

June 04, 2015

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.

Structural model of a human transfer-RNA (tRNA)
In the three-dimenstional structural model of a human tRNA, the nucleosides are depicted in orange and grey; chemical modifications are shown as coloured balls.

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).

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