After five decades of uncertainty, University College London researchers have finally devised a theoretical set of early Earth conditions under which RNA and amino acids could combine to form the origin of life, as presented in a new paper in Nature.
With RNA, a cousin of DNA, acting as the blueprint and amino acids as the building materials, life could have spontaneously formed under these specific conditions four billion years ago, the researchers demonstrate. Since the early 1970s, researchers have actively sought to understand how those two elements may have initially come together.
Building Proteins
“Life relies on the ability to synthesize proteins – they are life’s key functional molecules. Understanding the origin of protein synthesis is fundamental to understanding where life came from,” said senior author Professor Matthew Powner. “Our study is a big step towards this goal, showing how RNA might have first come to control protein synthesis.”
Ribosomes are an essential molecular machine that life uses to synthesize proteins. The instructions for that synthesis are carried by RNA, acting as a go-between for DNA and the ribosome. When the ribosome receives those instructions, it acts as a protein factory, building the required compounds from amino acids.
“We have achieved the first part of that complex process, using very simple 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,” Powner says.
Origins of Life: in Context
Scientists had made earlier unsuccessful attempts to create the first synthesis of life’s building blocks by using highly reactive molecules to connect RNA and amino acids. Unfortunately, the bonding molecules lack resilience and break down in water instead of permanently linking the intended subjects.
Rethinking the connection issue, the team behind the new research successfully employed a high-energy chemical compound called a thioester, in the form of a sulfur-bearing compound named pantetheine. Earlier theorists had suggested that these compounds may have played a role in the origin of life, and today they are recognized as playing important roles in various biological processes.
Tracking the reactions required specialized techniques to investigate the structure of molecules, including magnetic resonance imaging and mass spectrometry, due to the size of the action being below the range of visible light microscopes.
“Our study unites two prominent origin 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,” Powner said.
This paper isn’t the first the team has published revolving around pantetheine, as one they published last year demonstrated that conditions on the early Earth would be suitable for the compound’s synthesis. Such a finding bolstered the likelihood that pantetheine may have had an active part in the origins of life. The team’s innovation this time is in showing that RNA is capable of preferentially bonding to specific amino acids, forming the basis of the genetic code.
One Step Closer
“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 Powner.
“Imagine the day that chemists might take simple, small molecules, consisting of carbon, nitrogen, hydrogen, oxygen, and sulfur 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,” said lead author Dr Jyoti Singh.
The researchers say that their results bring such goals one step closer to fruition by demonstrating how amino acids and RNA could have contracted peptides in a natural environment. For the reactions to have occurred on the early Earth, the team suspects that pools or lakes would be the most likely locations, as ocean chemicals would be too diluted.
“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,” Singh concluded.
The paper, “Thioester-mediated RNA Aminoacylation and Peptidyl-RNA Synthesis in Water,” appeared in Nature on August 27, 2025.
Ryan Whalen covers science and technology for The Debrief. He holds an MA in History and a Master of Library and Information Science with a certificate in Data Science. He can be contacted at ryan@thedebrief.org, and follow him on Twitter @mdntwvlf.