At the heart of Life lies a powerful partnership: RNA gives the instructions, and proteins do the work. But how did this molecular matchmaking begin?
Amino acids, the building blocks of proteins, can’t build themselves. They need RNA, Life’s ancient instruction manual. Yet, for decades, scientists couldn’t figure out how these two first teamed up.
Now, in a breakthrough published in Nature, researchers have finally recreated this moment. Using simple chemistry that could’ve existed on early Earth, they linked amino acids to RNA. It’s like discovering the first page of Life’s cookbook. And it’s been missing since the 1970s.
Senior author Professor Matthew Powner, based at UCL’s Department of Chemistry, said: “Life relies on the ability to synthesise proteins – they are Life’s key functional molecules. Understanding the origin of protein synthesis is fundamental to understanding where Life came from.”
“Our study is a big step towards this goal, showing how RNA might have first come to control protein synthesis.”
“Life today uses an immensely complex molecular machine, the ribosome, to synthesise proteins. This machine requires chemical instructions written in messenger RNA, which carries a gene’s sequence from a cell’s DNA to the ribosome. The ribosome then, like a factory assembly line, reads this RNA and links together amino acids, one by one, to create a protein.”
“We have achieved the first part of that complex process, using elementary chemistry in water at neutral pH to link amino acids to RNA. The chemistry is spontaneous, selective, and could have occurred on the early Earth.”
In a recent study, researchers ditched harsh lab tricks and took a cue from Nature’s own playbook. They used thioesters, high-energy compounds that already play starring roles in modern metabolism (think Coenzyme A). These molecules gently “activated” amino acids, making them reactive enough to link with RNA.
Professor Powner said: “Our study unites two prominent origins of life theories – the ‘RNA world’, where self-replicating RNA is proposed to be fundamental, and the ‘thioester world’, in which thioesters are seen as the energy source for the earliest forms of Life.”
To get amino acids sizzling and ready to bond with RNA, scientists needed a special ingredient: pantetheine, a sulphur-rich compound that acts like a molecular marinade.
Last year, the same research team showed that pantetheine could be cooked up under ancient Earth conditions, no lab wizardry required. That makes it a strong contender for one of Life’s original prep tools, helping amino acids transform into thioesters, the reactive forms needed to start linking up with RNA.
“There are numerous problems to overcome before we can fully elucidate the origin of life, but the most challenging and exciting remains the origins of protein synthesis,” said Professor Powner.
Lead author Dr Jyoti Singh, from UCL Chemistry, said: “Imagine the day that chemists might take simple, small molecules, consisting of carbon, nitrogen, hydrogen, oxygen, and sulphur atoms, and from these LEGO pieces form molecules capable of self-replication. This would be a monumental step towards solving the question of Life’s origin.”
“Our study brings us closer to that goal by demonstrating how two primordial chemical LEGO pieces (activated amino acids and RNA) could have built peptides**, short chains of amino acids that are essential to life.”
“What is particularly groundbreaking is that the activated amino acid used in this study is a thioester, a type of molecule made from Coenzyme A, a chemical found in all living cells. This discovery could potentially link metabolism, the genetic code, and protein building.”
The study mainly looks at the chemistry involved, but the researchers believe the reactions they observed could have happened naturally in small bodies of water like ponds or lakes on early Earth. They don’t think these reactions would occur in the ocean, since the chemicals would be too spread out.
Because the reactions are extremely tiny, too small to see with a regular microscope, the team used advanced tools to study them. These included magnetic resonance techniques to understand how atoms are arranged in the molecules, and mass spectrometry to measure the size and structure of the molecules.
Journal Reference:
- Singh, J., Thoma, B., Whitaker, D. et al. Thioester-mediated RNA aminoacylation and peptidyl-RNA synthesis in water. Nature 644, 933–944 (2025). DOI: 10.1038/s41586-025-09388-y
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