New Study Uncovers m6A RNA Methylation’s Role in RSV Infection and Correlation with Autophagy
Respiratory syncytial virus (RSV) has long been a menacing force, causing severe respiratory infections in vulnerable populations such as young children, the elderly, and those with compromised immune systems. In fact, RSV has been ranked as the second leading cause of lower respiratory tract infection-associated deaths, resulting in a staggering number of cases and fatalities worldwide each year. Despite its pervasive impact, effective treatments have remained elusive. However, novel breakthroughs in the realm of RNA research offer new hope in the battle against RSV.
At the heart of this scientific progress lies the world of epigenetics, specifically the study of RNA methylation. RNA modification, an essential process beyond the genetic code itself, has surfaced as a pivotal post-transcriptional regulatory mechanism. Within this intricate landscape, more than 150 RNA modifications have been discovered, with methylation commanding the spotlight, constituting over 60% of all known RNA modifications. Of the various RNA methylations, N6-methyladenosine (m6A) has emerged as a star player, identified in a diverse range of RNA types from mRNA to ncRNA. This chemical alteration, regulated by an ensemble of methyltransferases, binding proteins, and demethylases, orchestrates a symphony of gene expression, protein translation, and developmental processes across organisms spanning yeast to mammals.
m6A has a far-reaching impact, influencing cell differentiation, cell cycle regulation, circadian rhythm maintenance, disease progression, and even viral infection and replication, among other things. In the context of RSV, scientists have begun to unveil its elaborate connection with m6A. This nexus was exemplified by a past study that illuminated the modification of RSV RNAs by m6A, enhancing the virus's replication and pathogenicity [1]. Yet, the plot thickens as we delve deeper into the relationship between m6A, RSV infection, and a fundamental cellular process known as autophagy. Autophagy, the cellular "clean-up crew," engulfs and degrades cellular debris, playing a crucial role in maintaining cellular health. It is also employed by host cells as a powerful defense tool against viral infection by initiating an innate immune response. A new study, situated at the crossroads of RSV infection and RNA methylation, revealed a captivating interplay [2].
In this investigation, researchers honed in on human lung epithelial BEAS-2B cell line, and the spotlight fell on the m6A demethylase FTO. FTO expression was observed to increase during RSV infection, leading to a decrease in total m6A modification levels within the host cells. Further analysis exposed a captivating network of m6A-related players, encompassing writers (METTL3/14, RBM15B), erasers (FTO), and readers (YTHDF1/2), collectively weaving a complex tale of interaction in RSV-infected cells. Intriguingly, DDIT3 surfaced as a central figure, showing significant upregulation during RSV infection and a positive correlation with FTO (and a negative correlation with METTL3/14, RBM15B, and YTHDF1/2). DDIT3, a member of the C/EBP family of transcription factors, has previously been associated with other viral infections and autophagy. Alongside this surge in DDIT3 expression were visible signs of autophagosome formation. The autophagy markers LC3B II/I and Beclin1 soared, painting a comprehensive portrait of autophagy induction.
Taken together, these findings highlight the link between m6A and autophagy, not only providing deeper insights into RSV infection but also elucidating potential avenues for therapeutic intervention. Simple yet high-throughput methods of assessing m6A would undoubtedly facilitate the development of novel drugs against this epigenetic target and its associated modifiers. Studies like this one benefit from robust quality assays such as EpigenTek’s ELISA-based EpiQuik™ m6A RNA Methylation Quantification Kit, which offers a sensitive, specific, reliable, and consistent means of directly measuring levels of m6A in total RNA via a convenient, microplate-based format.
References
Xue M, Zhao BS, Zhang Z, et al. Viral N6-methyladenosine upregulates replication and pathogenesis of human respiratory syncytial virus. Nat Commun. 2019;10(1):4595. Published 2019 Oct 9. doi:10.1038/s41467-019-12504-y
Li Z, Liu Y, Zhang L, et al. N6-methyladenosine modification contributes to respiratory syncytial virus infection. Heliyon. 2023;9(4):e15307. Published 2023 Apr 6. doi:10.1016/j.heliyon.2023.e15307
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Respiratory syncytial virus (RSV) has long been a menacing force, causing severe respiratory infections in vulnerable populations such as young children, the elderly, and those with compromised immune systems. In fact, RSV has been ranked as the second leading cause of lower respiratory tract infection-associated deaths, resulting in a staggering number of cases and fatalities worldwide each year. Despite its pervasive impact, effective treatments have remained elusive. However, novel breakthroughs in the realm of RNA research offer new hope in the battle against RSV.
