Gene translation more complex than expected

Researchers from Marvin Tanenbaum's group at the Hubrecht Institute have shown that the translation of genetic information stored in our DNA is much more complex than previously thought. This discovery was made by developing a type of advanced microscopy directly visualizing the translation of the genetic code into a living cell. Their study is published in the scientific journal Cell June 6th.

From gene to protein

Every cell in our body contains the same DNA, but different cells, like brain cells or muscle cells, have different functions. The differences in cell function depend on the parts of the genetic information (called genes) active in each cell. The genetic information stored in these genes is translated by specialized translation plants called ribosomes. The ribosomes read the genetic code and assemble the proteins according to the information stored in that genetic code, just like a factory that makes a machine from a plan. Proteins are the workhorses of our body and fulfill the functions encoded in our genes. For our cells and organs to function properly, it is essential that the genetic information stored in our genes is accurately translated into proteins. If the genetic code is not translated correctly, harmful proteins can be produced, which can lead to neurological diseases such as Huntington's disease.

The "reading frame" of genes

The genetic code is translated into groups of 3 letters, each word-like, which is translated into a single part of the protein. If a ribosome starts to translate the code to the wrong position, the 3-letter code can be changed. For example, the sentence below should read as follows:

"The man saw his new red car"

However, if a ribosome begins to translate this sentence a letter too late, the sentence would read as follows:

"A week ago"

In the case of the genetic code, this phenomenon is called "out of frame" translation. Sanne Boersma, a researcher at the Hubrecht Institute, explains: "As the example sentence illustrates, out-of-frame translation has a significant effect on the protein and usually results in a protein that behaves differently and may damage the cell. " Until now, it was difficult to know how the ribosome knew where to start translating the code and how often the ribosome was wrong.

A new method: SunTag and MoonTag

The researchers have developed a new method to visualize the decoding of our genetic information in living cells. They were able to mark different protein products of different colors and visualize the production of each type of protein using advanced microscopy. Each protein was labeled with the help of a specific tag called the SunTag tag and MoonTag, which she could see under a microscope (Figure). By combining MoonTag and SunTag, researchers could now see for the first time how many times the out-of-frame translation was done.

A big surprise

The researchers discovered that translation out of context was surprisingly common. In extreme cases, nearly half of the proteins built used a reading frame or a code different from the expected code. These surprising findings show that the genetic information stored in our DNA is much more complex than previously thought. According to this new study, our DNA probably encodes thousands of previously unknown proteins with unknown functions. Sanne Boersma: "Thanks to our study, we can now ask some very important questions: what do all these new proteins do, do they have important functions in our bodies or do they waste secondary products of translation that can damage our cells? "

Provided by
Hubrecht Institute