University of Maryland scientists have developed a method to determine the structures of large RNA molecules at high resolution, overcoming a challenge that has limited 3D analysis and imaging of RNA to only small molecules and pieces of RNA for the past 50 years.
The new method, which expands the scope of nuclear magnetic resonance (NMR) spectroscopy, will enable researchers to understand the shape and structure of RNA molecules and how they interact with other molecules. The paper on this work, which could lay the groundwork leading to targeted RNA therapeutic treatments for disease, was published today in the journal Science Advances.
“The field of nuclear magnetic resonance spectroscopy has been stuck looking at things that are small, say 35 RNA building blocks or nucleotides. But most of the interesting things that are biologically and medically relevant are much bigger, 100 nucleotides or more,” said Kwaku Dayie, a professor of chemistry and biochemistry at UMD and senior author of the paper.
Dayie and his team first demonstrated that their method could produce data and images equal to current methods by applying it to pieces of RNA from HIV containing 30 nucleotides, which had been previously imaged. They then applied their method to pieces of Hepatitis B RNA containing 61 nucleotides—nearly double the size of previous NMR spectroscopy possible for RNA.
Their method enabled the researchers to identify sites on the hepatitis B RNA where small molecules bind and interact with the RNA, which could help understand the effect of potential therapeutic drugs. The next step for the researchers is to analyze even larger RNA molecules.
Read the full article on the College of Computer, Mathematical, and Natural Sciences website.
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