It has been discovered that RNA strands, just 45 nucleotides long, carry out two key reactions required for self-replication. The molecule, a type of RNA enzyme, offers intriguing clues to understanding the origin of life: how the chemistry of inanimate objects on Earth before life began to self-replicate and evolve.
“Since the two reactions do not occur sequentially or in one pot, we have not yet reached the stage of self-replication,” explains the lead researcher. Eduardo Gianni They carried out the study with colleagues from Philip Holliger’s lab at the University of Cambridge, UK. “What we are describing is autosynthesis, the ability of RNA to copy itself and synthesize a complementary strand that encodes it. Neither of these reactions had been previously demonstrated with polymerase ribozymes.
Polymerase ribozyme is a type of RNA enzyme. RNA world hypothesis. This theory proposes that RNA molecules emerged from a chemical soup and developed the ability to encode genetic information and catalyze self-replicating reactions within protocells, before DNA and proteins evolved.
Although polymerase ribozymes do not exist in any known life forms, scientists have created polymerase ribozymes in the laboratory. They are known to catalyze the synthesis of other RNA molecules, suggesting an important role in the origin of life. However, because ribozymes typically have long nucleotide sequences and complex folded structures, it is highly unlikely that ribozymes could have copied themselves or appeared spontaneously on pre-biotic Earth.
According to Gianni, research on polymerase ribozymes has never been able to demonstrate self-replication. Scientists speculated that complex prebiotic chemistry and non-enzymatic replication must have enabled the emergence of large, complex ribozymes.
“We decided to take a leap of faith in the dark and see if we could obtain a new polymerase ribozyme strain that might have a higher potential for self-replication,” Gianni says. They used directed evolution techniques on a collection of 1 trillion random RNA sequences to arrive at a 45-nucleotide-long ribozyme called QT45.
Experiments in eutectic ice (a slimy mixture of water and salt that promotes polymerase activity and has been shown to be a plausible environment on pre-biotic Earth) revealed that QT45 can catalyze the synthesis of its complementary strand and copy itself. However, for copying, it took 72 days to reach a yield of only 0.2%.
Comment: “Incredibly slow” david lilya molecular biologist who studies ribozymes at the University of Dundee in the UK. “However, this is a good step on the road to proof-of-principle and demonstrates the key elements needed for the plausibility of the RNA world hypothesis.”
In the RNA world scenario, short RNA strands are much more abundant than long strands. Meanwhile, previous lab experiments testing spontaneous RNA polymerization have achieved lengths of about 20 nucleotides, which can then recombine to form QT45-long RNAs, Gianni explains.
“It significantly lowers the hurdles that need to be achieved non-enzymatically before ribozyme-catalyzed replication can begin,” Gianni says. “If this is a necessary pathway for the emergence of life, we can infer that it affects the overall probability of life arising spontaneously from pure chemistry, and that the probability is higher than before.”
Going forward, Gianni says the team would like to run the two reactions in one pot, ending the cycle of self-replication. “We also want to improve yields to a level where the system can sustain itself and start growing and evolving,” adds Gianni.