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By Stephanie Phelps
June 7, 2023
In recent years, scientists have uncovered a fascinating new area of research involving the modification of RNA molecules. Just like our DNA, RNA can undergo changes that alter its structure and function. These modifications, known as post-transcriptional modifications (PTMs), have been found to play crucial roles in the diverse functions of RNA within cells. So far, researchers have identified around 140 different PTMs in cellular RNAs, contributing to their remarkable structural diversity.
At the molecular level, PTMs can affect the stability of RNA molecules and reshape their higher-order structures. They also influence the interactions between RNA and proteins, DNA, or other RNA molecules. For example, the absence of specific modifications in certain types of RNA can disrupt vital cellular processes. In the case of viruses, RNA modifications have been observed on their genomes, but their biological significance is still largely unknown.
The presence of PTMs in viral RNA has been detected in various viruses, including Dengue virus, influenza, simian virus 40 (SV40), and human immunodeficiency virus type 1 (HIV-1). These modifications have been found to impact different steps of the viral lifecycle, such as replication, stability, and RNA splicing. Some viruses even encode their own enzymes to introduce these modifications, while others hijack cellular enzymes to modify their RNA.
Groundbreaking studies have shown that one specific modification, called N6-methyladenosine (m6A), can significantly affect viral RNA. For instance, m6A has been found to influence the replication and stability of HIV-1 RNA. Similar activities of m6A on viral RNA have been observed in cells infected by Zika virus (ZIKV), Dengue virus, and hepatitis C virus (HCV). These findings suggest that PTMs may play essential roles in virus-host interactions, allowing viruses to disguise their RNA and evade host defenses.
However, investigating RNA modifications in viruses has been challenging due to the lack of suitable analytical tools. Recently, researchers have developed advanced mass spectrometry (MS) approaches that enable the direct analysis of RNA strands, providing a more accurate characterization of PTMs. By applying this cutting-edge technology, scientists have made significant progress in uncovering the full landscape of PTMs in both cellular and viral RNAs.
In a groundbreaking study, researchers employed this analytical approach to explore the impact of viral infections on the epitranscriptome, the complete set of RNA modifications, of host cells. By comparing the modifications in infected cells to uninfected cells, they discovered a coordinated response mounted by the host to combat viral infections. Through their analyses, they also identified general PTM patterns as well as virus-specific modifications.
Furthermore, by examining viral genomes isolated from infected cells and virions, the scientists gained valuable insights into the vast diversity and dimensions of viral epitranscriptomes. These findings provided clues about the potential functions of PTMs during the viral lifecycle. To further understand the relationship between PTMs and cellular processes, researchers have conducted experiments to evaluate the effects of a cellular RNA helicase on RNA modifications. The study aimed to lay the foundation for a comprehensive understanding of the effects of viral infections on RNA modifications. By identifying common features and differences across different viruses, researchers hope to unravel the functional significance of viral epitranscriptomes and shed light on the intricate interactions between viruses and their hosts.
This research marks a crucial step forward in our exploration of RNA modifications in the context of viral infections. The findings not only expand our knowledge of the complex world of RNA, but also provide a promising framework for future investigations into the mechanisms underlying virus-host interactions. With further studies, we may uncover novel targets for antiviral therapies and gain a deeper understanding of how viruses manipulate host cells to their advantage.
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