A new study led by Northwestern University uncovers the mystery of how RNA molecules are folded to enter cells and perform specific functions. The breakdown findings could break down the understanding and development of treatments for RNA-related diseases, including spinal muscular atrophy and possibly even the novel coronavirus.
“RNA folding is a dynamic process that is fundamental to life,” said Julius B. Lucks of Northwestern, who led the study. “RNA is a very important piece of diagnostic and treatment design. The more we know about the complexity and complexity of RNA, the better we can design treatments.”
Using data from complex RNA experiments, the researchers generated the ever-driven films on data on how RNA folds as it is produced by cellular devices. By watching their videos of this folding happening, the researchers found that RNAs often fold in strange, perhaps unconscious ways, such as tying itself in knots – and then immediately unlocks itself to reach its final structure.
“Fractures occur in your body more than 10 quadrillion times per second,” Lucks said. “It happens every time a gene is expressed in a cell, but we know so little about it. Our films allow us to finally watch it happen for the first time. “
The research will be published January 15 in the journal Cell molecular.
Lucks is an associate professor of chemical and biological engineering at Northwestern’s McCormick School of Engineering and a member of the Northwestern Center for Synthetic Biology. He co-directed the work with Alan Chen, a professor of chemistry at the University of Albany.
While there are videos of RNA wrapping, the computer models that generate them are full of speculations and assumptions. The Lucks team has developed a technology platform that captures data on RNA folding as the RNA is made. His group then uses computational tools to mine and organize the data, revealing points where the RNA folds and what happens after folding. Angela Yu, a former Lucks student, fed this data into computer modules to generate accurate videos of the folding process.
“The information we provide the algorithms will help the computer models to correct themselves,” Lucks said. “The model produces accurate simulations that are consistent with the data. “
Lucks and his colleagues used this strategy to model an RNA complex called SRP, an ancient RNA found in all realms of life. The molecule is famous for its signature hairpin shape. While watching the videos, the researchers found that the molecule binds itself in a knot and binds itself very quickly. It then abruptly moves into the right hairpin-like structure using an elegant folding path called a mediated toehold movement.
“As far as we know, this has never been seen in nature,” Lucks said. “We believe that the RNA has evolved to bind itself from knots because if knots hold, it can inactivate the RNA. The structure is so essential to life that it has to come on. forward to find a way to get out of a knot. “
###
The study found, “Correspondingly reconstructing cotranscriptional RNA complex pathways from experimental data revealing rearrangement of non-native complex mediators,” supported by National Institutes of Health (award numbers T32GM083937, 1DP2GM110838 and GM120582) , the National Science Foundation (award numbers MCB1651877 and 1914567) and the Searle Fund of the Chicago Community Trust.
Disclaimer: AAAS and EurekAlert! they are not responsible for the accuracy of press releases posted to EurekAlert! by sending institutions or for using any information through the EurekAlert system.