JERUSALEM, Aug. 1 (Xinhua) – Israeli scientists have discovered when and where mistakes occur in the cellular manufacture of proteins, which may help with Alzheimer’s and cancer researches, the Weizmann Institute of Science (WIS) reported Thursday.
The researchers not only succeeded in measuring the rate of such mistakes, but also revealed that the DNA contains a “mistake manual” of sorts that dictates where these mistakes need to be avoided and where they may be tolerated or even welcome.
Some mistakes, for example, might cause misfolded proteins to aggregate in a cell, as happens in Alzheimer’s disease, whereas others may give a cell an evolutionary advantage.
Such errors can originate from spelling mistakes in the DNA, but much more common are mistakes occurring later, when the genetic message is copied and sent to the ribosome, the cell’s protein “factory.”
Using an innovative version of mass spectrometry method and advanced algorithms, the researchers discovered and analyzed all the mistakes that occur in protein production in a single amino acid cell - in yeast and bacterial cells.
It turned out that mistakes occur most commonly in the ribosome – that is, in the final “translation” stage of protein production.
Wrong amino acids are inserted into a protein at this stage at the average rate of one in about 1,000 amino acids (almost one mistake per protein). But the range is great, from one mistake in several dozens of amino acids to one in about 10,000.
The most surprising finding was that the distribution of these mistakes are much more common in proteins expressed in the cell in smaller rather than in larger amounts.
This is because more abundant proteins would clutter up the cell much sooner if they contained errors, so that the cell would not have survived evolution.
Moreover, within each protein, translation errors are much more common at positions that are less critical to the protein’s function and stability.
According to the scientists, the findings will make it possible to examine the impact of mistakes on neurodegenerative diseases, cancer, aging and evolution of the species.
