Decoding the cellular postcode system
In neurodegenerative diseases, the death of nerve cells leads to a variety of consequences. In Alzheimer's disease, for example, the mass death of nerve cells in the brain results in the loss of cognitive abilities. In amyotrophic lateral sclerosis (ALS), motor nerve cells die so that commands from the brain no longer reach the muscle cells in the body. Progressive paralysis is the result,
„Many of these diseases begin with the loss of nerve cell branches,
says Dr Marina Chekulaeva, head of an independent research group at the Max Delbräck Center's Berlin Institute for Medical Systems Biology (MDC-BIMSB). Chekulaeva assumes that misdirected messenger RNA molecules (mRNA) are responsible for this loss. The mRNAs contain the building instructions for important protein molecules that are also important for the interaction of nerve cells. If they do not arrive at their actual destination, the nerve cells lack an important function. Contacts between neurones are lost, nerve pathways are interrupted and the cells themselves die. A functioning post system for mRNAs is therefore a basic prerequisite for nerve cells to be able to carry out their important work.
„We know that there are hundreds to thousands of localised mRNA molecules in cells,
says Chekulaeva. „So we can assume that there are also mechanisms that bring the mRNAs to their destination.“ Nobody yet knows exactly how this cellular mail system works in detail. But there are clues: Back in the 1990s, US researchers discovered that a single mRNA molecule has a kind of postcode - a sequence at the back end of the mRNA. With its help, the transport systems, the cell's postmen, allocate the mRNAs to their destination. In the scientific journal „Nature Neuoscience“, Chekulaeva's team has now presented a method that can identify the postcodes of other mRNAs.
Mapping of thousands of mRNA sequences
The team led by Chekulaeva has determined the location of the mRNAs in the cell and used a specially developed method to identify the sequences that are relevant for their transport there. The special thing about our method is that it allows us to analyse thousands of RNA sequences simultaneously," says Samantha Mendonsa, one of the first authors of the study. „This allows us to identify the postcode for different localised mRNAs that assigns them to their destination.“
The researchers at the Max Delbrück Center are not only able to identify multiple, previously unknown postcodes. They have also created a tool with which the postal system in various other polarised cell types can be studied in detail.
The postcodes help us to decipher the entire postal system with all its transport molecules and receptors that are necessary for localised mRNAs to reach their destination,
says Chekulaeva.
This in turn can provide information about what goes wrong in the post-system of ALS patients, for example, when it comes to the loss of nerve cell branches and later entire motor nerve cells. In the future, the researchers hope to contribute to a better understanding of this neurodegenerative disease and even pave the way for new therapeutic approaches.
The above texts, or parts thereof, were automatically translated from the original language text using a translation system (DeepL API).
Despite careful machine processing, translation errors cannot be ruled out.