DNA (deoxyribonucleic acid) carries genetic information for the development and functioning of an organism. It contains the instructions for making proteins, which perform many different functions in cells. However, DNA doesn't just become a protein; it must go through several stages to reach the final modified product.
Brief introduction to the journey:
- DNA and transcription
- mRNA processing
- Translation
- Polypeptide
- Folding
- Functional protein
DNA is made of 4 hydrogenous bases: Adenine (A), Thymine (T), Guanine (G), Cytosine (C). These bases are organised in a specific order in the DNA, which is the genetic information. What can be hard to understand is how the sequence of bases can eventually determine the structure of a protein.
This journey begins in the nucleus with transcription. Transcription is when the DNA double helix structure unwinds to expose the required gene. An enzyme called RNA polymerase binds to a specific region near the gene called the promoter, and this basically signals where transcription should begin. The RNA polymerase moves along the template strand, and free RNA nucleotides come via complementary binding to make the pre-mRNA strand.
The base pairings:
A -> U (uracil)
T -> A
C-> G
G-> C
This product is initially pre-mRNA, as it is not the final mature mRNA. The process of transcription is useful as it ensures DNA remains inside the nucleus and the mRNA provides a copy of the instructions.
Now the pre-mRNA must turn into the final mature mRNA. The pre-mRNA contains sections which are not translated into the final protein, such as introns, and sections which are included in the mature mRNA, such as exons. This is when RNA splicing is carried out by the spliceosome, and the introns are removed, and the exons are joined together. Now that this has happened, the 5’ cap is added to the beginning of the mRNA to help protect the mRNA from exonucleolytic attack (essentially protects it from being broken down). Finally, the poly - A- tail is added, which is a sequence of adenine bases which are added to the other end of the mRNA. This helps increase mRNA stability and also prevents degradation. Now the mRNA is ready to leave the nucleus through the nuclear pores and enter the cytoplasm. Once the mRNA has entered the cytoplasm, it attaches to a ribosome, which is where the information in the mRNA can be converted into an amino acid sequence.
We have now reached the translation stage, which is where the message is turned into a protein. The ribosomes are made from ribosomal RNA and proteins, and they move along the mRNA and read its sequence. In the ribosome, the mRNA is read in groups of three bases, with each group being called a codon. Each codon relates to a specific amino acid or signals the end or start of translation. The start codon is usually AUG and codes for methionine, and after reading this, the ribosome continues reading the sequence. Then comes transfer RNA. Each tRNA molecule contains an anticodon, which is complementary to a codon on the mRNA. The tRNA molecules bring the correct amino acid to the ribosome, and the ribosome can then join the amino acids together using peptide bonds. This chain keeps growing as more amino acids are added until a stop codon is reached. Now that the process has stopped, the newly produced chain is released.
It is important to acknowledge how important an amino acid sequence is. It isn’t just a random chain of amino acids; it ultimately affects how the chain interacts with itself, as each amino acid has different properties. The sequence of amino acids will influence how the chain folds (and its 3D structure) and therefore its final function as a protein.
Translation has now produced a polypeptide chain (a long chain of amino acids); however, this chain isn’t necessarily functional yet, as it needs to fold into a particular 3D shape. To get to the 3D shape, there are many different structures. Starting with the primary structure, this is the exact sequence of amino acids - the polypeptide chain. This is determined by the genetic information. Then we have the secondary structure, which is when the polypeptide chains fold and are stabilised by hydrogen bonding. The main examples are alpha helices and beta sheets. Next is the tertiary structure, which is when the whole polypeptide folds into its overall 3D shape. This contains many more interactions than in secondary structures. Some include: hydrogen bonding, ionic interactions, hydrophobic interactions and disulfide bonds. Finally, there is the quaternary structure, which is made up of multiple polypeptide chains, and these chains come together to form a functional protein. Some examples of quaternary proteins are haemoglobin and catalase.
In the previous paragraph, we discussed the different levels of structure, and a key idea to understand is that structure determines function. A protein's shape determines what it is able to interact with. For example, an enzyme has an active site which can be 3-5 amino acids big, so it is incredibly small. However, it must be a specific shape so that the substrate can interact with the site, so the products can be released and reactions can occur.
Our bodies are very good at controlling many reactions and ensuring everything goes smoothly, but sometimes things can go wrong. Mutations can occur in the DNA, and this is a change in the DNA sequence. If this mutation occurs in a gene that codes for a protein, it can alter the mRNA sequence. This could then change the amino acid sequence. If you remember from earlier, the sequence is very important in determining structure, and structure is important in determining function…. Therefore, a mutation can have consequences. One mutation that presents challenges is mutations in the gene coding for beta-globin. This results in a change to the amino acid sequence of haemoglobin, which can affect the behaviour of red blood cells. This is called sickle cell disease. That is not to say that every mutation causes a problem, as some have little or no effect.
To wrap this up, DNA stores information using sequences of bases and this can then be transcribed into mRNA. The mRNA is transported to a ribosome, which turns the nucleotide sequence into an amino acid sequence, which then can be folded into a functional protein. The final structure that the protein takes will determine its function. So this seemingly simple sequence of bases can ultimately determine the behaviour of a complex molecule.
Chloe Tohme
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