Writer: Anouska Aluni
Editor: Sophie Rogers
If you’ve ever attended a biology lesson, you likely know something about the importance of proteins. They’re essential for muscle and tissue growth, digestion, immune defence… and almost every process that keeps organisms alive. Proteins are fundamental for life.
In modern cells, proteins are synthesised in two tightly controlled steps: transcription and translation. During translation, an enzyme called RNA polymerase reads a specific region of DNA and produces a complementary RNA copy. This process occurs in the nucleus, where DNA is protected. Instead, the RNA copy carries the instructions needed to synthesise a protein and can leave the nucleus, acting as a molecular messenger. Hence, it is known as messenger RNA (mRNA).
The mRNA then enters the cytoplasm, where it binds to the ribosome, where translation takes place. The ribosome reads the sequence of nucleotides and converts the genetic information into a sequence of amino acids, forming a polypeptide chain. This process is highly efficient and accurate as it is driven by enzymes and carefully controlled molecular interactions.
A key role in translation is played by transfer RNA (tRNA). For tRNA to participate in protein synthesis, it must first be chemically bonded to an amino acid in an activated form, forming aminoacyl-tRNA, which delivers the specific amino acid to the corresponding sequence on the mRNA strand. As translation proceeds, the growing chain of amino acids is temporarily attached to another tRNA, peptidyl-tRNA, which holds the peptide chain together as new amino acids are added.
But this raises a deeper question: how did protein synthesis first evolve? This process depends on the ability of amino acids to bind to RNA. Understanding how amino acids could have attached to RNA under prebiotic conditions, before enzymes existed, is essential to explaining how protein synthesis, and ultimately life, first evolved.
Confused? Don’t worry, you’re not alone – this question has also challenged scientists for decades.
Abiogenesis, or the origin of life theory, proposes that life arose from non-living matter. One key framework of this theory is the “RNA World Hypothesis”. This suggests that RNA was the original self-replicating molecule, storing genetic information and catalysing chemical reactions (ribozymes). Later in time, DNA took over as the hereditary molecule. This hypothesis suggested that protein synthesis, controlled by complex machinery and interactions between proteins and RNA, could have evolved in the early world due to RNA’s properties.
However, this hypothesis doesn’t explain the formation of amino acid-RNA complexes, which allows translation to occur. In water, amino acids preferentially react with other amino acids rather than with RNA. While short peptides may form spontaneously, this does not explain the highly controlled, enzyme-reliant, RNA-directed process seen in modern cells.
An alternative proposal is the “Thioester World Hypothesis”, which suggests that sulphur-containing compounds called thioesters provided both the energy and chemical reactivity needed for early metabolism. Thioesters are still essential to modern biology as important intermediates in biochemical reactions and metabolism.
Recently, chemists at UCL have provided experimental evidence supporting both of these hypotheses. In a study led by Professor Matthew Powner, researchers demonstrated that thioesters could selectively attach amino acids to RNA under prebiotic conditions. Professor Powner explains: “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.”
The research shows that two fundamental parts of protein synthesis – attaching amino acids to RNA and linking amino acids into a peptide chain – can be controlled chemically, in prebiotic Earth conditions, without enzymes. Thioesters allow amino acids to selectively bind to other amino acids. However, the presence of thioesters alone did not lead to peptidyl-RNA synthesis at all. A pH change and addition of hydrogen sulfide and ferrocyanide allows a chemical switch to occur, converting thioesters to thioacids, which prevents aminoacylation (a chemical process by which amino acids are attached to RNA), allowing for non-ribosomal peptide synthesis to occur. This suggests that early protein synthesis could have been chemically viable long before the evolution of enzymes or ribosomes.
Previously, Professor Powner’s lab also demonstrated that pantetheine, a sulphur-containing compound and a key fragment of Acetyl-CoA, can be synthesised from nitriles in water. Pantetheine is essential in completing the synthetic pathway from nitriles to aminoacyl-thiols. This allowed them to aminoacylate RNA and synthesise peptidyl-RNA in water.
By uniting the RNA World and Thioester World Hypotheses, the research conducted by Professor Powner’s lab offers a glimpse into the origins of life on Earth, highlighting the possibility of its gradual emergence through a few key chemical reactions.
As UCL celebrates its 200th anniversary, pioneering research like this highlights its enduring role as a home for disruptive thinking.
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