From hard-working newspaper reporter to world-saving superhero, Clark Kent makes the transition to Superman in just a few seconds. Now, scientists have discovered that human cells are home to their own hidden superheroes, secretly helping us to fight off a range of viruses.
The latest study, led by the MRC-University of Glasgow Centre for Virus Research in collaboration with the Rosalind Franklin Institute, has uncovered intriguing new insights into how our cells respond to viral infection.
The research, published in the journal Molecular Cell, reveals the surprising behaviour of a group of key proteins that are usually found in the nucleus of our cells. When they join forces with an RNA, called U2, their day job is helping to create new proteins. However, researchers now believe this cellular team may also be responsible for protecting us against viral threats.
New research has shown that this RNA protein team, known as U2 snRNPs, temporarily halts its normal role when a cell is infected. When a virus is detected, the cellular team moves outwards from the nucleus of a cell to an area called the cytoplasm to defend against infection. Surprisingly, the RNA protein team then takes on a new ‘superhero’ role and gathers in areas where the virus is replicating, preventing it from multiplying.
The research team describe the proteins as transforming into to molecular roadblocks, attaching themselves to viruses and stopping them from replicating, ultimately helping to defeat any infection.
Dr Wael Kamel, first author of the study, said: The observation that there are other RNA-mediated antiviral cellular mechanisms beyond the famous RNAi is extremely exciting. Imagine several large stone boulders blocking a road. It would definitely create a problem for the proper circulation of cars. From a molecular perspective, a similar traffic jam would occur when a virus tries to replicate its viral RNA while the U2 snRNP protein group is attached to it."
To carry out the study the team infected cells in the lab with the mosquito-borne viruses such as Sindbis virus, as well as the virus coxsackievirus B3, which comes from the same family of viruses as the common cold and can produces cardiomyopathy in infants. The researchers were able to show that the Protein-RNA team known as the U2 snRNP behaved in the same way with these viruses, suggesting a broad-spectrum antiviral activity.
Professor Alfredo Catello, senior author on the study, said: “We believe that this is an intrinsic mechanism by which cells delay virus infection to allow other antiviral efforts such as the production of interferon to be put in place. We foresee that this antiviral mechanism could be manipulated to explore new therapeutic approaches against viruses”.
The discovery is especially timely, coinciding with the 2024 Nobel Prize for the discovery of miRNA, marking the third Nobel Prize awarded for RNA-guided silencing complexes after those for CRISPR (2020) and RNAi (2006).
By shedding light on these host-virus interactions, the study paves the way for innovative approaches to antiviral therapies and further deepens our understanding of the complex dialogue between viruses and their hosts.
The study ‘Alphavirus Infection Triggers Selective Cytoplasmic Translocation of Nuclear RBPs with Moonlighting Antiviral Roles’ is published in Molecular Cell. The work was funded by the European Research Council and the Medical Research Council (UK).
**Enquiries: ali.howard@glasgow.ac.uk or elizabeth.mcmeekin@glasgow.ac.uk**
**First published: 12 December 2024**