Life depends on a partnership between RNA, which stores instructions, and proteins, which do the work of building and running cells. But how this partnership began has long puzzled scientists. To make a protein, constituent amino acids must be linked in the order encoded by RNA. Today, a complex biological machine called the ribosome handles this task — but only after each amino acid is first “loaded” onto an RNA adapter. The catch is that the enzymes responsible for this loading are themselves proteins, creating a chicken-and-egg puzzle that has intrigued chemists for decades.

A new study in Nature offers a glimpse of how this riddle might have been resolved. Researchers at University College London found that simple molecules called aminoacyl-thiols can link amino acids to RNA without enzymes.

Think of amino acids as beads and RNA as the thread. In cells today, enzymes act as skilled hands to string them together. The team showed that, in the right conditions, with aminoacyl-thiols the beads can fasten themselves to the thread in plain water, much like on the early earth.

More strikingly, this aminoacyl-thiol chemistry favours RNA over other, more reactive molecules, which is an unexpected selectivity that has astonished chemists.

“It’s remarkable that RNA, which is relatively unreactive, undergoes aminoacylation in water despite the presence of more reactive species,” said Tom Sheppard, a chemist at UCL not involved in the study.

He added that the chemistry appears robust across many amino acids and simple enough that other labs should be able to reproduce it. By giving RNA a clear chemical advantage, aminoacyl-thiols may have paved the way for the first steps of protein synthesis.

For scientists who study life’s beginnings, the discovery is more than a clever bit of chemistry: it’s a breakthrough that ties two of life’s building blocks together in conditions that could have existed billions of years ago.

“Previous research often looked at either how peptides (chains of amino acids) could form or how nucleotides could form, but rarely how the two might interact,” Sheppard said. “What makes this work significant is that it shows RNA and amino acids talking to each other directly, without any intermediary.”

“This opens a lot of exciting directions to investigate the origins and evolution of protein translation,” Matthew Powner, who led the work, said.

Selectivity and surprises

What struck the researchers the most was not just that the reaction worked but that it showed such uncanny precision. The amino acids latched onto RNA ends in a way that reflects how life does to this day.

Powner said the reactivity was the heart of the discovery: “If I had to pick only one thing that was the most astounding, it would be the unexpected reactivity between aminoacyl-thiols and RNA that led to unprecedented selectivity at neutral pH.”

Sheppard pointed out another interesting facet. Thioesters were once thought to be simple precursors to peptides, but the study found that they are not good at making peptides directly. “Instead,” he said, “they may have played a different role: guiding amino acids onto RNA.”

Even more intriguingly, the team discovered that a simple chemical switch could separate two key stages of modern protein synthesis. With thioesters, amino acids preferentially attach to RNA. But when those same molecules are converted into thioacids, the chemistry flips, favouring the formation of peptide bonds instead. That means the two steps of protein building — RNA-charging and peptide-linking — can be carried out in the same solution but under distinct chemical modes of activation.

The team did not stop there. They also explored where these aminoacyl-thiols might have come from. Their experiments suggested they could form from simple precursors such as nitriles and thiols, even under frigid conditions that concentrated the ingredients and sped up reactions.
This implies the chemistry linking amino acids to RNA may not have required rare settings: it could have unfolded in the ponds or frozen pools of a young earth.

Both Powner and Sheppard agreed that this chemistry is just a starting point. The peptidesmade so far are very short, and figuring out how to extend them will be the next challenge.