rna-protein analysis

A Live-Cell NanoBRET Assay Shines Light on Toxic RNA–Protein Interactions in Myotonic Dystrophy

Posted on by Johanna Lee
How NanoBRET works image.

RNA doesn’t just carry genetic instructions—it also interacts with proteins to regulate nearly every aspect of gene expression, from splicing to translation. When those interactions go awry, the consequences can be devastating. In myotonic dystrophy type 1 (DM1), the most common adult-onset muscular dystrophy, a toxic RNA repeat expansion hijacks a critical protein called MBNL1, trapping it in nuclear clumps called foci. This leads to widespread splicing defects and progressive muscle wasting. But studying these toxic interactions inside living cells—and finding small molecules that can disrupt them—has been a significant challenge.

A recent study led by the Scripps Institute may have a solution. The study introduces a NanoBRET™ assay that can monitor the interaction between the expanded CUG RNA repeats and MBNL1 protein in real time, in live cells. Their findings demonstrate how this platform can be used not only to detect disease-driving RNA–protein complexes but also to identify small molecules that break them apart.

Continue reading “A Live-Cell NanoBRET Assay Shines Light on Toxic RNA–Protein Interactions in Myotonic Dystrophy”

RNA-Protein Interactions: A New Frontier for Drug Discovery

Posted on by Jordan Villanueva

Almost 90% of the human genome is transcribed into RNA, but only 3% is ultimately translated into a protein. Some non-translated RNA is thought to be useless, while some play a significant yet often mysterious role in cancer and other diseases. Despite its abundance and biological significance, RNA is rarely the target of therapeutics.

“We say it’s undruggable, but I would say that ‘not-yet-drugged’ is a better way to put it,” says Amanda Garner, Associate Professor of Medicinal Chemistry at the University of Michigan. “We know that RNA biology is important, but we don’t yet know how to target it.”

Amanda’s lab develops systems to study RNA biology. She employs a variety of approaches to analyze the functions of different RNAs and study their interactions with proteins. Her lab recently published a paper describing a novel method for studying RNA-protein interactions (RPI) in live cells. Amanda says that with the right tools, RPI could become a critical target for drug discovery.

“It’s amazing that current drugs ever work, because they’re all based on really old approaches,” Amanda says. “This isn’t going to be like developing a small molecule kinase inhibitor. It’s a whole new world.”

Continue reading “RNA-Protein Interactions: A New Frontier for Drug Discovery”