Striking new videos show how RNA – the genetic molecule that tells cells how to make proteins – gets tangled up in crazy lumps, only to disintegrate themselves in the last second, and in a way surprise scientists.
High-resolution videos depict a bouncing conga line of nucleotides, the building blocks of Royal army; Single strands of RNA grow longer, these nucleotides dance and fold into different three-dimensional shapes, first in a deformation and then in a second. Once fully assembled, RNA assumes its final shape, which describes 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 undone for this final shape to emerge.
“So RNA has to come out of this,” study author Julius Lux, an associate professor of chemical and biological engineering and a member of the Center for Synthetic Biology at Northwestern University. RNA will not function correctly if it is implicated in the wrong knot, meaning a knot that meets its final shape along the way, he said. “What a surprise how it got out of that trap. … It was only discovered when we had high-resolution videos.”
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In the new study, published on January 15 in the journal Molecular cell, Luck and his colleagues generated their videos of RNA using experimental data and a computer algorithm. The goal was to learn how to zoom in as RNA, both to better understand basic cell biology and to pave the way for better treatment for RNA-related diseases.
In experiments, the team used a specific type of RNA, called Signal Recognition Particle (SNP) RNA, an evolved ancient molecule found in all states of life. They used this RNA as a model because it performs a fundamental function in many cell types.
How to zoom Cells Producing this RNA, the team used chemicals to halt the manufacturing process. So as soon as nucleotides were added to RNA, the researchers paused and then recorded how those nucleotides already interacted with others in the lineup, and what size they all formed together. By capturing data from several individual RNA molecules, the team developed a snapshot of how RNA typically builds itself through time.
These snapshots act as individual frames that will become their final videos of RNA formation. This is where the computer model came from. The algorithm essentially encapsulates individual frames in mini-films and fills in the gaps between frames with the most likely nucleotide interactions. In these videos, the team saw how RNA was entangled in complex lumps that, if left bound, would render the entire molecule useless.
“It folds in this trap state, and it lives there,” Luck said. SNP RNA is intended to form in a signature “hairpin-like” shape, and these traps occur along the way. But as more nucleotides are added in this sequence, new nucleotides open the knot by displacing the nucleotides that have penetrated inside.
“This last little nucleotide is like a trigger” that allows the entire RNA to pop into the correct depolarization, Luck said. Think of the final fold in an origami project, which suddenly transforms a piece of paper into a beautiful butterfly. In the video, the nucleotides exposed themselves to a purplish purple knot, and the dark pink nucleotides help release them, Luck noted.
Learning how RNA tangles and unangles are important in understanding how cells function and how proteins are formed; Research can help detect diseases where RNA does not function properly or cannot form a specific protein, such as spinal muscular atrophy, And infectious diseases such as COVID-19 Which are caused by RNA virus, According to a statement.
A major question is whether RNA can dissociate itself from most of these lumps, or whether auxiliary proteins are sometimes required to make this process easier. It is possible that some proteins act as so-called “RNA chaperones” and help mold the molecule to its final form, Lucas said. He stated that it could be a combination of the two, although at this point, it is speculative.
Originally published on Live Science.