| The next step in the gene expression process is the reading of the mRNA or decoding the mRNA by translating it into a protein. This process is called Protein Synthesis or Translation and is executed by the Ribosomes. These organelles, which have been very well studied, consist of two subunits, a ´larger´ and a ´smaller´ subunit, which normally stick together. There is a large number of factors involved in translation, which are loosely bound to ribosomes and can dissociate. Since translation is divided into the ´Initiation´, the ´Elongation´ and the ´Termination´ step, there are specialized factors for all three steps. |
| The first step in translation is the Initiation. This step is the most important step for translation regulation and therefore also the step, which is deregulated in cancer cells. Let´s have a closer look. Prior to initiation the ribosomes have to separate into the individual subunits (done by an initiation factor). We learnt that mRNA has a structure called ´Cap´. This is very important in the initiation step, because a complex of some factors binds to the cap end. It was shown that the overexpression of the actual cap-binding protein (eIF4e) leads to the transformation of normal to cancer cells in a particular assay used to demonstrate this. Cancer cells isolated from patients also show higher levels of this protein. The function of this protein complex is to allow the binding of the small ribosomal subunit to the mRNA. Once this ´Initiation complex´ is accomplished the larger subunit joins. The ribosome now moves over the mRNA and keeps moving and moving until there is an AUG codon for the amino acid methionine, which is the start codon (if you want to refresh your memory regarding the genetic code go back to Genetic Code). |
| At this stage of protein synthesis we have to introduce a new compund called transfer RNA or tRNA. This RNA is the actual decoder substance. As the name says, it is an RNA and it has a certain structure similar to a cloverleaf. The important point here is that this RNA can recognize the codon and carries at the same time the amino acid belonging to that particular codon (AUG corresponds to methionine). For every codon there is one tRNA and since there are 61 codons for amino acids (plus 3 nonsense codons) there are also 61 tRNA´s. The tRNA for methionine with UAC (UAC::AUG) as its antisense codon now joins the initiation complex. |
| After stabilizing this complex the Elongation Phase is initiated when the ribosome moves on for one more codon. Let´s assume this codon is a GGG (amino acid Glycine) codon. The tRNA with the anticodon CCC carrying a Glycin now is incorporated in this complex. The amino acid Methionine (Met) is then transferred to Gly and forms a peptide bond. We have now a peptide consisting of Met-Gly. In the next step the ribosome moves on one more codon and the ´empty´ tRNA-Met exits the complex and the whole process repeats itself until the ribosome reaches a nonsense codon, which does not code for any amino acid and therefore there is no tRNA. At this point the whole complex dissociates into the single components and the mature protein is released. Let´ now review this whole series of events again animated. |
| What comes next? In the next lesson protein modifications will be introduced. By the way, wondering how this is related to cancer? Translation is important as a drug target. |
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