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Striking new videos show how RNA – the genetic molecule that tells cells how to build proteins – tangles in insane knots as it forms, only to unravel at the last second, and then in a way that surprised scientists.
The high-resolution videos illustrate a bouncing conga line of nucleotides, the building blocks of RNA; As the single strand of RNA grows longer, these nucleotides dance and twist into different three-dimensional shapes, wiggling first into one conformation and then into another. When fully assembled, RNA takes on its final form, which dictates how it can interact with other molecules and proteins in the cell.
But along the way, RNA can get trapped in “knots” that must be untied for that final shape to emerge.
“So RNA has to come out of it,” said study author Julius Lucks, associate professor of chemical and biological engineering and member of the Center for Synthetic Biology at Northwestern University. RNA will not function properly if it gets trapped in the wrong node, that is, a node that interferes with its final shape, he said. “What was surprising was how he got out of that trap.… It was only discovered when we got the high resolution videos.”
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In the new study, published Jan.15 in the journal Molecular cell, Lucks and his colleagues generated their RNA videos using experimental data and a computer algorithm. The aim was to zoom in on how RNA is formed, both to better understand basic cell biology and to pave the way for better treatments for RNA-related diseases.
In the experiments, the team used a specific type of RNA called signal recognition particle (SNP) RNA, an ancient evolutionary molecule found in all realms of life. They used this RNA as a template because it performs a fundamental function in many types of cells.
To zoom in on how cells to build this RNA, the team used chemicals to interrupt the build process. So, as new nucleotides were added to the RNA, the researchers paused and then recorded how those nucleotides interacted with others already in the range and what shapes they all formed together. By capturing data from many individual RNA molecules, the team developed snapshots of how RNA typically builds up over time.
These snapshots served as individual frames in what would become their final RNA training videos. This is where the computer model came in. The algorithm essentially chained the individual images into mini-movies and filled the spaces between the images with the most likely nucleotide interactions. In those videos, the team noticed how the RNA got tangled up in complex knots that, if tied together, would render the whole molecule useless.
“It falls back into that trap state, and it kind of just stays there,” Lucks said. SNP RNA is believed to form in the shape of a “hairpin”, and these traps seem to get in the way. But as more and more nucleotides are added to the sequence, the new nucleotides rush to unravel the knot by moving the nucleotides tangled inside.
“That last little nucleotide is like a trigger” that allows all of the RNA to appear in the correct conformation, Lucks said. Think about the last fold of an origami project, which suddenly turns a crumpled piece of paper into a pretty butterfly. In the videos, the nucleotides highlighted in dark purple tie together and the dark pink nucleotides help release them, Lucks noted.
Learning how RNA tangles and disentangles is essential to understanding cell function and protein formation; research can also help fight diseases in which RNA does not work properly or a specific protein cannot form, such as spinal muscle atrophyand infectious diseases such as COVID-19[female[feminine which are caused by RNA viruses, according to a statement.
A big question is whether RNA can primarily disentangle itself from these nodes or if it sometimes needs helper proteins to facilitate the process. It’s possible that some proteins act as “RNA chaperones” and help sculpt the molecule into its final form, Lucks said. He added that it could be a combination of the two, although at this point it is speculative.
Originally posted on Live Science.
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