Breakthrough RNA mapping method by HIRI researchers

SHIFTR allows unbiased protein identification on RNA regions in live cells.

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HIRI and Broad Institute scientists have created a groundbreaking tool to map RNA-protein interactions globally without genetic modifications. This method, detailed in Nucleic Acids Research, unveils the interplay crucial for cell balance and the virus-host struggle. It avoids the need for genetic alterations, providing an unbiased approach to studying individual RNA regions and their interactions.

When viruses like SARS-CoV-2 infect cells, they use RNA elements to recruit proteins for their gene expression. Researchers from HIRI and the Broad Institute created SHIFTR. This mass spectrometry method allows unbiased mapping of proteins interacting with specific RNA sequences in live cells without genetic modification. This breakthrough helps understand viral RNA interactions, revealing potential vulnerabilities in replication and aiding in designing antivirals.

Jens Aydin is a PhD student in Mathias Munschauer’s research group. The study’s first author in Nucleic Acids Research said, “With this new tool we can determine the interactions for practically every cellular RNA and regulatory element within these RNAs. This can fundamentally change how we look at RNA in the cell—a crucial milestone.”

The research team used SHIFTR to explore SARS-CoV-2 replication, focusing on crucial RNA regions. They uncovered new interactions, including with proteins related to viral RNA biogenesis. These discoveries may lead to innovative antiviral therapies. In the future, SHIFTR can aid in understanding cellular transcriptome regulation in health and disease, revealing new drug targets. Additionally, the platform can characterize how RNA therapeutics, like mRNA vaccines, interact with cellular regulatory machinery, inspiring the design of optimized RNA-based drugs.

HIRI’s groundbreaking method, SHIFTR, marks a significant advancement in RNA research. Its application in mapping specific RNA interactions in live cells contributes to our understanding of viral replication. It opens new avenues for studying cellular processes and developing targeted therapies. 

The findings have implications for both virology and broader biomedical research, promising future breakthroughs in understanding and treating various diseases.

Journal reference:

  1. Jens Aydin, Alexander Gabel, et al., SHIFTR enables the unbiased identification of proteins bound to specific RNA regions in live cells. Nucleic Acids Research. DOI: 10.1093/nar/gkae038.

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