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Amino acids as catalysts in the emergence of RNA

The question of how life could have emerged is one of the most long-standing mysteries in science. In a new study, the laboratory of LMU Professor Dieter Braun has uncovered an unexpected form of molecular collaboration between the fundamental components of life. The researchers found that amino acids—simple, abundant molecules on early Earth—can actively promote the polymerization of RNA under mild, prebiotic conditions.

This finding challenges long-held assumptions about the "RNA world" at the origin of life and suggests that life may have started through a more balanced interplay between RNA and amino acids.

Biopolymers composed of different building blocks are essential for living systems. RNA, a molecular thread comprising four bases, creates the blueprint for the production of proteins from amino acids. These proteins, in turn, drive all biochemical reactions inside cells.

"Life as we know it today is a complex collaboration of two informational polymers: RNA and proteins. The big question is: Why and how did they join forces at the beginning of life, even before Darwinian molecular evolution began?" asks Braun, principal investigator of the study.

End of RNA world hypothesis?

The researchers, whose study has now been in Nature Communications, demonstrated that the formation of the RNA molecules increased by up to 100-fold in the presence of amino acids. This process is attributed to a form of acid-base catalysis driven by the amine group of amino acids. At an alkaline pH, amino acids exist in both neutral and negatively charged forms, enabling them to shuttle protons in the polymerization reaction that forms RNA from ribonucleoside 2′,3′-cyclic phosphates—a prebiotically plausible starting point.

"Our findings close a critical gap in our understanding of early evolution. Until now, we knew how proteins were made by the catalytic machinery of RNA, but now we're beginning to understand how the building blocks of proteins can also help RNA form. It's a mutual dependence of two core molecules of life that reshapes our view of life's molecular origins," says Saroj Rout, lead author of the study.

This catalytic ability of amino acids, even in their simplest form and without being incorporated into complex proteins, suggests a clear functional role in amplifying RNA formation. Notably, the reaction occurs at room temperature, with moderate alkalinity and low salt concentrations, conditions that are favorable for long-term RNA stability and replication.

Alkaline conditions important for emergence of life

Intriguingly, the same elevated pH that facilitates amino acid-catalyzed RNA synthesis also supports RNA templating, where short strands of RNA guide the assembly of complementary sequences via ligation. This results in autocatalytic replication networks, ultimately laying a robust foundation for Darwinian evolution.

According to the researchers, these results emphasize the importance of alkaline environments, which have often been overlooked in previous origin-of-life experiments. Similar alkaline environments are found on volcanic islands, for example.

"Our findings provide a compelling revision to the RNA world hypothesis," says Braun. "They open up opportunities for cooperation between RNA and amino acids in the early stages of evolution, bringing us closer to recreating the first steps of life in a laboratory setting."