‘RNA can do things which we have never seen before’: New study challenges assumptions about what RNA was up to at the dawn of life
Scientists have long wondered when RNA began life on Earth 4 billion years agoIt can only form small, simple structures. But new research shows that naturally occurring RNA molecules can also adopt large, sophisticated geometries, such as filaments and cages. Now, scientists wonder whether the structures existed at the beginning of life.
According to an idea known as RNA world hypothesisRNA-based life-forms preceded modern life-forms that use DNA and proteins. royal armyA molecular cousin of DNA, it still plays a role in modern cells but does not serve as the primary genetic material. By comparison, primordial species used RNA to store genetic information and catalyze reactions as stand-in enzymes.
Proteins eventually came to dominate as enzymes, perhaps because they could fold more diverse data As much as RNA can. This is because proteins are made up of 20 types of subunits, called amino acids, each with a unique structure, whereas RNA is made up of only four subunits, called nucleotides, which all adopt the same shape.
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Scientists originally thought that only proteins were diverse enough to assemble into large structures, but a new paper shows that RNA – although more limited in its diversity – also has the ability to form these large configurations. The research was posted on a preprint server biorxiv July 1 and has not yet been peer-reviewed.
“We show that RNA can do things we’ve never seen before,” said the study’s co-author. lin huangAn RNA biologist at Sun Yat-sen University China. “This shows that RNA could assemble into all kinds of shapes at the time of the origin of life,” he told Live Science.
Huang and his colleagues hypothesized that RNA molecules could bind together if they had sequences that folded into a “kissing stem loop.” This occurs when an RNA strand folds on itself, forming a structure that resembles a loop in a shoelace. If loops of different RNAs bind together, or “kiss,” the molecules could join and form larger complexes, the researchers proposed.
After sifting through a series of RNA sequences, the researchers found a family of RNA molecules encoded by bacteriophages – viruses that infect bacteria – that form these loops. They purified many of these RNA molecules in the laboratory, allowed them to assemble in a dish, and then captured their structures using cryo-electron microscopy.
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They found that some RNA molecules formed long filaments. These resemble protein-based filaments such as the cellular cytoskeleton, a scaffold that participates in many functions, including shaping and moving the cell.
Other RNA molecules assembled into cages as large as those of common viruses. Some of these took the form of an icosahedron – a 3D shape made up of 20 equilateral triangles and resembling a soccer ball. including many viruses herpesvirusThey package their genome into protein-based icosahedra called capsids. This raises a question: Can RNA-based capsids package genomes in an RNA world?
The RNA structures assemble into icosahedra as large as the protein-based virus capsid.
(Image credit: Lin Huang)
This work shows that RNA had the ability to assemble into these elaborate structures during the RNA world, Huang said, but it does not prove that this actually happened.
“I certainly think the environmental parameters are a question,” Anna MedvegiEötvös Loránd University, an evolutionary biologist in Hungary, told Live Science in an email. “Could these structures have formed in the environment in which the hypothetical RNA world existed?” said Medvegi, who was not involved in the new work.
If scientists could recreate these environmental conditions at the beginning of life, such as high temperature and low pHAnd we’re still seeing these structures take shape, he said, which will strengthen the theory that they could exist in the RNA world.
Although the RNA cages and filaments were large, Huang’s team prepared them using only short RNA strands, each no more than 200 subunits in length. Long RNAs are sensitive to breakage, Medvegi said, so if shorter strands can assemble into these structures, it offers more possibility that these multi-stranded molecules could form in the RNA world.
Another question is whether these elaborated RNA complexes are currently assembled inside the bacteriophage-infected bacteria from which they were obtained. So far, Huang’s team has only seen these structures in a laboratory dish, so they needed to determine whether factors inside the bacteria, such as proteins, would either inhibit or enable their formation inside the cells.
Huang believes that in addition to providing insight into the beginning of life, these RNA cages may have potential applications in biotechnology. Efforts are underway to use DNA by folding it intodna origami” to deliver drugs into cells, and Huang thinks DNA’s older cousin, RNA, may one day play a similar role in therapy.
Ren, Y., Zhang, Z., Chen, K., Li, M., Xie, Y., Bai, T., Huang, B., Xiao, B., Westhoff, E., Lilly, DMJ, Wang, J., Miao, Z., Wei, X., and Huang, L. (2026). Structural assembly for the RNA world. bioRxiv. https://doi.org/10.64898/2026.07.01.735769
