Researchers have made a significant advance in understanding one of biology’s greatest mysteries: how two essential molecules of life first connected over four billion years ago. Proteins, built from chains of amino acids, serve as the workhorses of living organisms, forming tissues and carrying out countless functions. Yet, they cannot pass on the instructions for making themselves.
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That task falls to RNA, which functions as the messenger and translator of genetic information in all living cells today. The enduring puzzle has been how these two very different molecules initially linked, setting in motion the events that produced the genetic code and, ultimately, life as we know it.
“RNA molecules communicate information between themselves in a highly predictable and extremely effective way, but RNAs do not inherently communicate with the amino acids that they need to control in protein synthesis,” explained Prof Matthew Powner, senior author of the new study. “How and why these molecules first became connected has been an unresolved question for decades.”
Earlier laboratory attempts to recreate this chemistry faced obstacles: amino acids often reacted with each other instead of RNA, and unstable aqueous conditions caused the reactions to break down.
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Powner’s team approached the problem differently. By linking amino acids to a sulphur-containing chemical group called a thioester—a high-energy bond still used by cells today—they found the molecules reacted spontaneously and selectively with RNA. Remarkably, the natural structure of RNA guided the amino acids to the precise position at the end of the RNA strand where they must attach for protein synthesis.
This discovery provides a plausible chemical pathway for life’s most fundamental processes to begin without complex catalysts such as enzymes.
“These molecules are very simple and likely existed on early Earth,” said Powner. While the oceans would have been too dilute for these reactions to occur efficiently, nutrient-rich pools, ponds, and lakes could have offered ideal conditions.
The research also unites two long-standing hypotheses on life’s origins: the ‘RNA world’, which positions RNA as the principal driver, and the ‘thioester world’, in which high-energy thioesters powered early metabolism. Looking ahead, Powner aims to “elucidate the origins of life’s universal genetic code”. From there, scientists hope to determine exactly how and where life began on Earth.
“Scientists will build an experimentally validated set of reactions capable of forming a ‘cell’,” he said. “These cells will not only evolve but reveal the origins of life’s universal structures and organisation. This work will provide the information needed to rationally evaluate how and where life began on our planet.”
