Study finds viruses rely on diverse RNA traits to pack their genomes with precision

Researchers from the San Diego State University and Michigan State University shed new light on how viruses meticulously pack their genetic equipment – a breakthrough that could help researchers design antivirals and genic therapies.

The team’s conclusions, which are published in the Proceedings of the National Academy of Sciencesreveal how a combination of molecular properties allows viruses to selectively bring their own RNA in protein shells called capsids while ignoring the specific concurrent genome of a host cell. Like molecular armor, capsides protect the genetic material from a damage virus and help it sneak into host cells.

Know how viruses pack their RNA with high selectivity – a feat obtained with more than 99% precision by certain viruses – could help scientists design their own versions of capsids in the laboratory and to exploit them as powerful scientific tools.

“From the health point of view, synthetic capsides can be used to create antivirals that target RNA packaging, which can have an impact on humans, vegetable and animal agriculture, as well as veterinary medicine,” said Kristin Parent, director of the Cryo-Em installation of MSU and author of the latest article.

The last breakthrough is the result of a collaboration between Spartan researchers and those of the Garmann Lab at the State University of San Diego, which examines the complex molecular choreography behind viral replication, infection and evolution.

“Some RNA viruses are built from less than 200 molecules,” said Rees Garmann, assistant professor in the Department of Chemistry and Biochemistry of SDSU and the main author of the new study.

“And yet, they are capable of accomplishing remarkable exploits, such as replicating in astronomical number and building precise nanometric structures.”

The host with the most

To illustrate the amazing quantities of viruses found on our planet, Parent offers its students this breathtaking illustration: if you collect two handfuls of lake Michigan, you would hold more viruses than there are humans on earth.

Among these viruses, the most abundant types are bacteriophages or phages – viruses that infect and reply within bacteria. In their new study, the researchers examined a phage called MS2, which attacks E. coli.

Viruses are based on molecular machines from other cells to be reproduced. When MS2 attaches to a bacteria, it injects its own genetic material, forcing the host cell to assemble viral copies.

During this process, viral layer proteins assemble around viral RNA to form a capsid, which protects genetic cargo. With 180 identical layer proteins arranged to make 20 different sides, the resulting virus looks a bit like a football ball or a game game.

Finally, when the hosted host cell, a new generation of these phage copies is published.

For researchers like Garmann and Parent, the question was how the phage can recognize its own genome and wrap it so efficiently, especially when RNA mixes with the competitive genetic material from the host inside the cell.

“About 99% of the particles that we see at the end are perfectly formed viral copies, it is therefore a process of high fidelity,” said Parent, who is also a professor in the Department of Biochemistry and Molecular Biology of MSU.

RNA origami

Compared to the emblematic double propeller of DNA, the RNA is simple bit. This means that it can form complex secondary structures such as bulges, curls and hair pins.

Previously, the researchers thought that a particular structure called a TR STEM loop acted as a packaging signal for MS2. You could consider this as a molecular panel indicating where the viral RNA packaging should start.

To see which other factors can influence packaging, researchers have systematically scrambled the MS2 genome, producing RNA constructions with unique properties. These included molecules of variable shape, length and sequence.

Like watching finished products deploy a mounting chain after major changes to the factory floor, the team then analyzed the capsid packaging results to determine the impact of these RNA adjustments.

More specifically, they were able to see unique and often surprising capsid packaging results – too small viral particles, and even those that have ineffective forms.

What the researchers finally discovered is that MS2 Coat proteins alone are very capable of selectively wrapping viral RNA, and that a diversified group of RNA properties, not only the well -known TR loop, had a disproportionate impact on the process. This included the length of the RNA, the sequence and various rod and loop structures making a collective difference.

Thanks to their conclusions, the team helps to rewrite our understanding of how certain viruses carry out their impressive RNA catch -up exploits. With synthetic capsides and the new genetic cargo, these same molecular mechanisms can be exploited for the greatest good – of generation of genes and vaccines at the next generation of RNA -based therapies.