Cellular Defense Against Genetic Mistakes: Party is Over for Proteins
No biological process is perfect. Cells, much like people, make mistakes. Lynne Maquat and researchers at the University of Rochester Medical center have uncovered a critical step during nonsense mediated decay (NMD), the process by which cells monitor and prevent genetic mistakes.
Our genetic material is composed of deoxyribonucleic acids (DNA), which are modified into ribonucleic acids (RNA). Messenger RNA (mRNA) contains genes that code for specific proteins, and like a good messenger, delivers this information into translation, where the mRNA is converted into proteins. Proteins in turn, make up the body's structures and control its processes. If a protein is not translated correctly, its function is changed or it doesn't work at all. The world of genetic diseases is full of dysfunctional and non-working proteins.
The translational process isn't flawless. However, cells have developed ways of preventing mistakes during protein synthesis. Nonsense mediated decay (NMD) prevents the expression of aberrant proteins by degrading them.
Published in Cell, the study found that before proteins can be degraded by NMD, protein building on the faulty mRNA must be actively shut down, kind of like how a demolition crew would shut down a factory before destroying it, by removing its workers and turning off all machinery.
Maquat and researchers figured out exactly how protein building machinery gets turned off. Protein building is controlled by phosphorylation (the attachment of a group of molecules called phosphates). Attaching phosphates to a particular protein called human UPF1 acts like an "off" switch; the process shuts down protein building.
"One implication of these results is that we have a new target by which the decay of faulty mRNA can be prevented," said Maquat.
Preventing the destruction of faulty mRNA has potential implications for curing genetic diseases. For example, if a genetic mistake occurs in a gene that codes for an essential protein, and the mRNA containing this gene is destined for degradation, researchers might be able to halt this process.
By stopping the degradation of the mRNA containing the essential protein, methods could then be designed to ensure that protein-building machinery is turned on again to make the essential protein. However, much more research lies ahead before the process of NMD can be manipulated. Until then, we'll have to rely on good old cellular defense.
Written by Nadia Ramlagan
Reviewed by Muhammed Ziadh, Pooja Ghatalia
Published by Pooja Ghatalia