In a previous blog, we looked at DNA, genes and proteins. This blog dives deeper into this area of biology and focuses on how proteins are made from our genes. If you haven’t read the first blog, you can read it here.
How is our DNA used to make proteins?
Our DNA lives inside the control centre of our cells, called the nucleus, and it’s not able to leave this centre. However, the machinery needed to make proteins is outside the nucleus, in the cytoplasm of the cell, so how can we get the instructions for the protein out of the nucleus to make it?
Imagine there is a recipe in a book in a library that you want to use, but you can’t borrow the book. You can’t bake the cake in the library as there’s no oven, so you need to find another way to take the recipe home. You could photocopy it and take the copy home to make the cake.
This is what our cells do to the instructions in our genes. They make a copy of the genes which can leave the nucleus and be used by the machinery to make the proteins. This photocopy is called RNA.
While DNA has two strands, like a twisted ladder, RNA only has one strand, like half of the ladder. This is so it can leave the nucleus of the cell and the instructions can be easily read by the machinery that makes the proteins.
How is RNA used to make proteins?
The DNA is copied to RNA and this is able to leave the nucleus so that the protein machinery in the cytoplasm can make the proteins. DNA is made up of sections which contain instructions to make substances like proteins, called exons, and sections which don’t have any instructions but are still needed for other things, called introns. The exons make up the recipe and the introns are like adverts in the middle of the recipe. When the DNA is photocopied to the RNA, exons and introns are included in the copy. The introns can make the instructions hard to read so they need to be removed.
This is just one of the important jobs that proteins do within our cells. The RNA copy of DNA moves in the cytoplasm of the cell and this is where introns get removed by specialist proteins that can ‘cut’ them out of RNA.
Once the introns have been ‘cut’ out of the instructions, another protein acts as a glue and ‘sticks’ the exons back together in the same order. It’s this piece of RNA, without the introns, that is used to make a protein.
When the RNA instructions have been stuck back together, another protein attaches to read the instructions. It moves along the RNA and processes the instructions to find out what amino acids to collect and in what order they should be. These amino acids are the building blocks of the protein that is being made.
You can think of this like following instructions to make a necklace. You read the instructions to know which colour beads to use and in what order they should be. This is the same as the protein reading the instructions to find out which amino acids to use. The beads form the necklace, just like the amino acids form the protein.
Once the amino acids have been collected and joined together in the right order, the protein moves away from the RNA and is reused to read more instructions. When the amino acid chain has been made, the instructions break down and are either recycled for next time or destroyed. The chain is separated from the protein and gets folded into the final 3D structure that the protein has. You can see this process in the video below.
How is this linked to MND?
Research has suggested that there a number of proteins which are involved in the development and progression of the disease. Some of these proteins are made incorrectly because of changes in our genes. This means that they can’t carry out their jobs as they should and this can lead to many different problems in the cell. As well as not working properly, sometimes these incorrect proteins can build up and form clumps which become toxic to cells. For example, some people with MND have a change in a gene called SOD1 which means that the SOD1 protein is not made properly and can’t do its job anymore. The SOD1 protein forms toxic clumps inside the neurons and causes damage to them.
Some proteins in MND are made correctly but no longer work as they should because they lose their functions or become less effective at their jobs. For example, a protein called TDP-43 can be made correctly but loses its function in MND as it moves to the wrong part of the cell. It moves from the nucleus, where it carries out its work, to the cytoplasm. It can’t do its job in the cytoplasm so it builds up and forms toxic clumps which contribute to the damage of neurons in MND.
There are many different changes that can happen to genes in MND which affect how proteins are made and work within neurons. In a future blog in this series, we’ll explore some of these changes in more detail and discuss how they cause damage to neurons and play a role in the development of MND.
Keep an eye out for more Back to Basics blogs soon and in the meantime you can follow the latest updates in MND research on our website and by following us on twitter/X.
