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Researchers from the Helmholtz Institute for RNA-based Infection Research (HIRI) in Würzburg and the Broad Institute of MIT and Harvard have introduced a groundbreaking tool, named SHIFTR, capable of globally mapping direct interactions of individual RNA regions without genetic modification. This innovative method, described in the journal Nucleic Acids Research, presents a game-changing approach to study the interplay between ribonucleic acid (RNA) and proteins in live cells.
The intricate dance between RNA and proteins is crucial not only for maintaining cellular balance but also in the ongoing battle between viruses and their hosts. The tool’s significance is underscored by its potential to unravel the complex regulatory RNA elements exploited by RNA viruses, including the notorious SARS-CoV-2, during infection.
Traditional methods required genetic modifications or tags on target RNA for comprehensive mapping, but SHIFTR overcomes this limitation. The technique employs mass spectrometry to facilitate unbiased and thorough mapping of proteins interacting with specific RNA sequences, providing region-specific insights in living cells.
Mathias Munschauer, leader of a research group at the Helmholtz Institute Würzburg, explained, “Until now, it has not been possible to study the interplay between proteins and individual RNA regions in live cells without genetic manipulation. Our method, called SHIFTR, finally delivers this and is easy to execute, too.”
Jens Aydin, a PhD student in Munschauer’s research group, emphasized the transformative potential of SHIFTR in the study of RNA in cellular contexts. “This can fundamentally change the way we look at RNA in the cell — a crucial milestone,” stated Munschauer.
The researchers applied SHIFTR to delve into the replication process of SARS-CoV-2, examining different sequence regions within the virus’s RNA produced during infection. The study unveiled previously unknown interactions with proteins linked to the biogenesis of viral RNAs, offering new avenues for antiviral therapies.
SHIFTR’s versatility extends beyond virology, opening avenues to understand cellular transcriptomes in health and disease. Researchers foresee its application in characterizing how RNA-based therapeutics interact with cellular regulatory machinery, potentially influencing the design of optimized RNA-based drugs, including mRNA vaccines.
The study received support from the Helmholtz Young Investigator Group Program, the European Research Council (ERC), and the FOR-COVID Research Network, underlining the collaborative effort to advance our understanding of RNA-protein interactions and their implications for various biological processes.
