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Breaking the code of how viruses invade cells

Understanding the role that cellular microRNAs play in targeting viruses – and how viruses can express their own microRNAs to invade cells – could be key to developing new infection-fighting therapies. The RegulRNA project has been at the cutting edge of this research.

Health

Ribonucleic acid (RNA) is a molecule that plays various roles in the coding, decoding, regulation and expression of genes. Cells use messenger RNAs to transmit their genetic information, microRNAs are used to regulate gene expression and many viruses encode their genetic information using an RNA genome. There are around 2 000 different microRNAs in the human genome. They control genetic messages in the cell by binding to messenger RNAs together with a protein. “Although we know a lot about RNAs and their role in the context of viral infections, we know much less about the control of the regulatory RNAs themselves,” says European Research Council (ERC) grantee Sébastien Pfeffer from the French National Centre for Scientific Research (CNRS). “In other words, how are the regulators regulated?”

Evolution of viruses

This has been the focus of the RegulRNA (Modulation of RNA-based regulatory processes by viruses) project. Pfeffer used his ERC grant to look in particular at microRNAs, building on some previous work. “I discovered a few years back that some viruses express their own microRNAs, which are then used to target host genes,” he explains. “By binding to cellular messenger RNAs, the virus can hijack cells and adapt them to their own advantage. This is what viruses do.” In this latest project, Pfeffer wanted to better understand the complex role that microRNAs play in viral infections, the factors involved in generating them, and how some viruses evolve to express their own microRNAs.

Identifying targets for therapy

Pfeffer used different viruses as models to investigate the behaviour of microRNAs. A combination of techniques ranging from bioinformatics to cellular biology were used in order to gain a comprehensive view of how RNAs are regulated during viral infections. “Cells can use microRNAs to target the virus, but viruses can also use microRNAs to target the cell,” notes Pfeffer. “In our research for example we found a microRNA in the brain that can bind to viral RNA.” Preventing such microRNAs from binding with the virus could be one viable strategy to fighting infection. The project also looked at the behaviour of a herpes virus responsible for the development of some cancers. “We also know that some microRNAs are produced and can play a role in the cancer process,” Pfeffer points out. “If we can understand the process by which viral microRNAs are expressed, then again, we have something we can target to fight infection.” Significant steps have also been taken towards identifying the early signs of viral infection. When viral RNA enters a cell, it is recognised by the cell as a danger. “Identifying all the cellular proteins involved in this recognition could again be a way to help cope with viral infection,” adds Pfeffer. The project, currently in the process of validating its findings and due for completion in December 2020, could have implications for the current global health crisis. “Our research is still a work in progress, but we are of course interested in linking our findings to tackling COVID-19,” concludes Pfeffer. “We’ll be looking into this as soon as we have access to our laboratory again.”

Keywords

RegulRNA, microRNA, cells, viruses, infection, biology, cellular, COVID-19, cancers

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