Thursday, March 29, 2012

Hidden patterns in genes direct protein production

One of the most fundamental processes in biology is translation of genetic information into proteins, the building blocks of life. Cells have specialized machinery that read specific parts of the genetic code, called genes, and use that as a template to create an intermediate string of code that is consequently used by other cellular machines that turn the instructions into proteins. Effectively, DNA functions as a blueprint, and the intermediate form, called RNA is used as a messenger to tell the protein makers what to do. Scientists from the University of California in San Francisco have found hidden instructions in the messenger RNA that have a large impact on the speed by which cells produce proteins. Because proteins are used for basically all cellular processes, the findings may have big consequences for our understanding of elementary processes of life.

Protein production
Building blocks (bases) are green. Red
and blue show the backbones
of each DNA string.
DNA is constructed of four building blocks called A, T, C and G, and it consists of two strings of information that are entwined with each other. That means the four building blocks are paired: A binds to T, and C pairs with G. For example, when one string reads AGCA, the other string would be TCGT. RNA copies are made from genes by creating a complementary string of code. If we look at the example again, it means that reading AGCA would mean creating a TCGT strand. However, RNA uses a building block called U instead of T, which means it will read UCGU. Thereafter, the messenger RNA (mRNA) is transferred out of the cell's core where the DNA is safely stored, and proceeds to the ribosomes, tasked with producing proteins from individual components called amino acids. They use the mRNA as instructions by reading it in triplets: a set of three building blocks corresponds to one amino acid being built into a protein.
Transcription: making an mRNA copy of a gene on the DNA. Translation: After transporting the mRNA out of the nucleus, ribosomes can read the code and build in an amino acid for every triplet, creating a polypeptid, or string of amino acids.
Hidden message
Because RNA is read in triplets, called codons, and there are four different types of building blocks, it means that there are 64 different combinations. However, there are only 21 individual amino acids found inside our cells. That means different codons can result in the same amino acids being built in, and scientists have long thought it makes no difference as to which triplet is used: as long as they correspond to the same amino acid, the resulting protein is the same. Experiments from the University of California revealed that this may not be the case. When one block of a triplet is changed, but still reads the same amino acid, it can impact the speed by which proteins are built. Therefore, it appears that there is more information than previously known inside these codons: they are not simply different versions of the same thing when coding for the same amino acid. To further illustrate that, experiments in bacteria revealed that it is possible to pause the production process by switching triplets for seemingly redundant ones. The ability to pause the production is something a specific set of codons possesses.

Proteins start off as strings of amino acids,
and then fold themselves in various steps
to the required form, which determines
their function.
Scientists claim that changing a building block can lower the production speed to 10 percent of the original, which means it significantly impacts the number proteins becoming available to perform their job inside the cell. Because cells use proteins for basically all processes, it greatly impacts cellular physiology. And if it happens on a large scale, it could even affect how tissues and organs function, though this remains to be proven. It is clear that the findings challenge a paradigm that has upheld itself for about 50 years, as RNA building block triplets do not seem to be redundant at all. Nevertheless, what mechanism underlies the rather big change in protein production speed is as of yet unknown.

It is interesting to find out whether these differences in protein production speed are associated with diseases, which is likely to be one of the next steps in this study. Additionally, it may be possible to speed up industrial production of proteins using this knowledge: because every form of life uses DNA to store information, we can use bacteria or yeast to make useful proteins for ourselves. Genetic modification allows us to build human genes inside a bacterium, which consequently produces it the same way as a human being would have done. Optimizing the genetic code by selecting the 'best' triplets could make this process a lot faster and thus cheaper.

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