What is a nonsense mutation?
A nonsense mutation causes a pre-mature stop codon to appear in the gene, causing the protein to end its translation earlier than expected, resulting in a truncated copy of the protein.
Nonsense mutation, usually leads to a genetic disorder.
From a mutated gene into a mutated protein
Many of our genes contain blue prints to generate proteins. The proteins are assembled inside our cells via the proteins' building machines.These machines receive the genetic data (the blue prints) as an input and use the data to build proteins. A mutation inside the gene will translate into a mutated protein, which can lead to a genetic disorder.
The protein building machines are called Ribosomes, understanding their inner work is important for nonsense mutations.
Introduction to genetics
Just in case you need, we created a short introduction into genetics, made for parents.
I Am A Ribosome
I am a Ribosome, I build proteins in your cells. In order to build proteins, I need assembly instructions. These instructions reside in the genes.
Each assembly instruction must include two basic markers. It must mark the start point - from there I start to read the genetic data and assemble the protein, and it must mark the end point, so I know when to stop. Since the genetic data "codes" for instructions, we don't call it marks, we call it codons.
Every gene that builds proteins contains a start and stop codon.
A Premature Stop Codon
A premature stop codon occurs when there is an error, such as a genetic mutation. Somewhere along the genetic data the mutation caused a stop codon to appear before the expected real stop codon. The result is a protein that is not fully built as it should be. The Ribosome stops the production of the protein in the middle of the process and the result may be a genetic disorder.
Nonsense Mediated Decay
You already know most of the mechanics of nonsense mutations, but to really complete the puzzle we need to introduce you to another key process. This is the nonsense mediated decay. For short we call it NMD.
Genetic assembly instructions, that carry a premature stop codon, will not always reach the ribosomes. The NMD process in our cells, tries to filter out genetic instructions that contain premature stop codons.
A mutation caught by the NMD won't reach the Ribosome
You Nailed It !
While we simplified the complexities that exist in real life, armed with the above knowledge you should be able to better understand the mechanics behind nonsense mutations and why is it so important to group together.
Nonsense mutation medications work on the Ribosome and the NMD processes in the cell: processes in the cell that are not related to specific gene. Read-through medications will cause the Ribosome to ignore the premature stop instructions while NMD inhibitors will cause the NMD to work less efficiently. The result would be an increase of the missing / truncated proteins. This can benefit a large number of disorder, unrelated to the gene where the mutation occurs.