A large study, published this week, highlighted that COVID-19 causes brain atrophy and damage but how this happens is yet unknown.

A comprehensive study revealed that COVID-19 may cause gray matter loss in the brain, most notably in areas of the brain involved in smell and memory processing.

But why and how COVID-19 shrinks the brain remains a mystery.

Now, a new study published today may help understand the cause.

mRNAs (messenger RNAs) are essential for protein synthesis. Their unique structure at the start of the chain, known as a cap, serves two purposes. It not only shields mRNA from degradation, but it also plays an important role in how messenger RNA creates proteins.

The initial few nucleotides of an mRNA can include tiny embellishments called methylation in addition to the cap structure. These are found in mammals as well as some of their pathogens, such as SARS viruses and trypanosomes, but their function is unknown.

Although scientists have known about these mRNA modifications for almost 45 years, their impact on mRNA function is still unknown. This is due to the fact that scientists have yet to demonstrate what happens when methylation in mRNA is ‘knocked out,’ or eliminated from animal model organisms.

A knockout model utilizing fruit flies (Drosophila) was successfully developed by scientists from the universities of Birmingham, Oxford, Nottingham, and Warwick, according to a report published in Nature Communications. That means scientists were able to demonstrate what happens when the flies lack the two enzymes required for methylation.

They discovered that, while the changed flies survived, the two enzymes were crucial in the animals’ reward learning process. The capacity of these flies to learn the link between a certain odor and a sugar reward was impaired.

“The study shows us that mRNA modifications have important functions in the brain,” explains lead scientist Dr Matthias Soller of the University of Birmingham’s School of Biosciences, “Even though these flies are alive, they are not very capable of learning essential survival skills.”

Professor Rupert Fray of the University of Nottingham, who is one of the paper’s co-authors, previously discovered that cap alterations in mice are very dynamic.

The researchers discovered that these changes helped in the transfer of mRNAs to synapses, which are the points where neurons communicate.

“This learning phenotype opens many new questions,” says Professor Scott Waddell of Oxford University’s Centre for Neural Circuits and Behaviour, “Although we do not yet know the detailed nature of the underlying neuronal dysfunction, it is reminiscent of the genetic disease associated with Fragile X Mental Retardation Protein FMRP, which also involves RNA biology and is known to produce defects in synapse development and plasticity.”

“Analysing the cap modifications is very challenging,” adds says Dr. Irmgard Haussmann of Birmingham City University, “and further technical hurdles need to be taken to look at modifications in specific mRNAs.”

“This is highly relevant as SARS and other viruses that have their own cap methylation enzyme, “says Dr Nathan Archer of the University of Nottingham School of Veterinary Medicine and Sciences, “but it is not really understood what role this plays in virus-host interactions.”

The team’s next step will be to delve more into the mechanism by which the modified mRNA can alter protein expression related to reward learning and virus spread.

Source: 10.1038/s41467-022-28549-5 

Image Credit: Getty

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