The mystery of life’s origins continues to puzzle scientists. How did complex molecules form and persist without breaking down? Researchers at ORIGINS, a Munich-based Cluster of Excellence, have uncovered a potential mechanism that may have allowed the first RNA molecules to stabilize in the primordial soup. When two RNA strands combine, their durability and longevity significantly increase.
It is believed that life on Earth began in water, possibly within a tide pool that was isolated from seawater at low tide but submerged by waves at high tide. Over billions of years, complex molecules such as DNA, RNA, and proteins developed in this environment before the first cells eventually emerged. Nonetheless, the exact process through which this occurred remains a mystery.
“We know which molecules existed on the early earth,” says Job Boekhoven, Professor of Supramolecular Chemistry at the Technical University of Munich (TUM). “The question is: Can we use this to replicate the origins of life in the lab?” The team led by Boekhoven at the ORIGINS Cluster of Excellence is primarily interested in RNA. “RNA is a fascinating molecule,” says Boekhoven. “It can store information and also catalyze biochemical reactions.”
The prevailing belief among scientists is that RNA was likely the first complex molecule to form. However, a major challenge is that active RNA molecules are made up of hundreds or even thousands of bases and are highly unstable.
When exposed to water, RNA strands rapidly disintegrate into their constituent parts through a process called hydrolysis. This raises the question: how could RNA have survived in the early primordial environment?
In a laboratory experiment, researchers from TUM and LMU used a model system of RNA bases that have a higher tendency to bond compared to naturally occurring bases found in our cells today.
Due to time constraints, the team urgently sought a fast answer. They introduced these quick-bonding RNA bases into a watery solution, supplied an energy source, and observed the length of the resulting RNA molecules. The outcomes were discouraging, as the formed strands of up to five base pairs only persisted for a few minutes.
However, the results differed when the researchers introduced short pre-formed RNA strands first. The unbound complementary bases swiftly bonded with this RNA through a process called hybridization. Double strands consisting of three to five base pairs were established and remained stable for several hours. “The intriguing aspect is that double strands prompt RNA folding, potentially rendering the RNA catalytically active,” explained Boekhoven. Consequently, double-stranded RNA offers two advantages: an extended lifespan in the primordial soup and the foundation for catalytically active RNA.
The formation of a stable double-strand in the primordial soup is a fascinating possibility we are currently exploring. There is potential for RNA molecules to form their own complementary strands, leading to the creation of a stable double strand.
Furthermore, the evolutionary advantage of double-stranded RNA, particularly in the formation of protocells, could have played a crucial role in the origin of life. These double-stranded protocells could provide stability and prevent the merging of contents, allowing individual protocells to develop unique identities and contribute to evolution.
Job Boekhoven hopes to enhance our knowledge of how the initial RNA molecules were formed and stabilized in the future.
“Some people regard this research as a sort of hobby. During the Covid-19 pandemic, though, everyone saw how important RNA molecules can be, including for vaccines,” says Boekhoven. “So, while our research is striving to answer one of the oldest questions in science, that’s not all: we’re also generating knowledge about RNA that could benefit many people today.”
Journal reference:
- Christine M. E. Kriebisch, Ludwig Burger, Oleksii Zozulia, Michele Stasi, Alexander Floroni, Dieter Braun, Ulrich Gerland & Job Boekhoven. Template-based copying in chemically fuelled dynamic combinatorial libraries. Nature Chemistry, 2024; DOI: 10.1038/s41557-024-01570-5