One of the primary functions of DNA is to serve as a set of instructions for protein assembly. Given that there are twenty amino acids, and only four nucleotides in DNA, the DNA is read as three base groups, with each group of three letters coding for a specific amino acid (or alternatively 'stop'). The generation of protein from DNA is under numerous controls and has several steps.
- DNA must be transcribed to RNA
- RNA must be translated to protein
Ribonucleic Acid (RNA) is a string of nucleotides that is similar to DNA with two major differences:
- The sugar which forms part of the 'backbone' is ribose, not deoxyribose. The extra hydroxyl group in RNA allows it to be degrade more easily.
- Uracil (U) replaces thymine (T) as one of the nucleotides; uracil being the unmethylated form of thymine.
Uracil and thymine are closely related in metabolism, and drugs which target one may also affect the other. 5-fluorouracil (5FU) is a common chemotherapy agent that interferes with thymine synthesis (restricting DNA repair) and is also incorporated into RNA causing structual abnormalities
RNA is usually found as a single strand in the cell, but has the ability to form complex structures by folding on itself. This is important for the non-protein coding RNAs which have regulatory functions within the cell.
Promotion of gene transcription
The helical DNA is typically wrapped around histones to prevent tangling (and prevent unwanted gene activation). In order for a gene to be transcribed, it must be made available for transcription proteins (RNA polymerase). This is accomplished by gene regulating proteins, which bind to the gene regulating strands near the gene and:
- Cause structual changes in histones to expose the strand
- Attract the the required proteins to begin transcription
Once the strand is exposed, it is processed by RNA polymerase, which opens the hydrogen bonds between the complementary DNA strands, and creates a chain of RNA nucleotides. Each RNA strand begins and ends with a 5' and 3' untranslated region, which is an important signal for other cell enzymes that allows them to recognise the RNA as messenger RNA.
Post transcription changes
The pre-messenger RNA dissociates from the DNA strand and undergoes further modification in spliceosomes. These contain small nuclear RNA molecules (snRNA), which removes the introns from the strand. Messenger RNA may also be degraded if it interacts with complementary micro-RNA molecules, small 20-30 base pair structures that attach to specific RNA sequences and target them for degredation. The final messenger RNA travels out of the nucleus and reaches ribosomes for translation.
Translation of RNA to protein
Translation involves reading the RNA strand (four possible letters) and converting it to a polypeptide (twenty possible bases). As discussed above, each group of three bases forms a codon which translates to an amino acid. Some amino acids are associated with several different codons. Stop codons cease RNA translation and allow the finished protein to leave the ribosome.
Translation is accomplished by transfer RNA (tRNA), small molecules which contain a group of three RNA bases (complementary to the desired codon) and the matching amino acid. As the mRNA passes through the ribosome, matching tRNA molecules 'fit' to their complementary strands. The amino acid groups are united and the polypeptide is created. The nucleotide portion of the tRNA molecules is trimmed off to complete the protein.
Proteins, which are simply a long chain of amino acids, undergo various folding procedures to arrive in their final shape. This folding is influenced by the amino acids, some of which attract or repel other amino acids. The process of folding is not completely understood but it is possible that changes in folding may also result in the proteins with the same amino acid structure, but different shape and function.