The quest to decipher how dormant molecules might have sparked life brings researchers closer to their goal. A team has developed a method using partially replicable RNA molecules, suggesting that genuine self-replication could eventually be achieved.

RNA is a pivotal molecule in the discussion of life’s origins, as it can store information like DNA and catalyze reactions akin to proteins. While neither function is perfect on its own, the dual capability has led many scientists to theorize that life originated with self-replicating RNA molecules. “This was the molecule that governed biology,” says James Atwater from University College London.

Nonetheless, engineering self-replicating RNA molecules is a challenging task. RNA can form double helices similar to DNA, which can also be copied in a similar manner. By separating the two helices and adding RNA nucleotides to each strand, one could theoretically produce two identical helices. However, the binding between RNA strands is so strong that it complicates their separation for replication.

Recently, Attwater and his team found that a trio of RNA nucleotides (triplets) can be tightly bonded, preventing the strands from re-zipping. “Three is the sweet spot,” Attwater elaborates, noting that longer combinations are prone to errors. Thus, in their methodology, the team mixed RNA enzyme double helices with the triplet sequences.

By acidifying the solution and heating it to 80°C (176°F), the helices can be separated to allow for triplet pairing. When the solution is then made alkaline and cooled to -7°C (19°F), the highly concentrated liquid remaining as water freezes activates the RNA enzymes, which then bind the triplets together to form new strands.

Currently, researchers have succeeded in replicating RNA enzymes of up to 30 nucleotides in length from an original strand of 180 nucleotides. They believe that enhancing enzyme efficiency could lead to full replication.

Attwater highlights that this “very simple molecular system” possesses intriguing characteristics. One is the potential correlation between triplet RNA sequences and the triplet code that dictates protein sequences in modern cells. “There may be a connection between the biological mechanisms employed for RNA replication and the way RNA is utilized in present-day biology,” he explains.

Additionally, the team has identified that the triplet sequences most likely to facilitate replication exhibit the strongest bonding. This suggests that the earliest genetic code may have consisted of this set of triplets, which adds another layer of interest.

Researchers contend that the conditions required to support this process might naturally occur. Given the need for freshwater, it’s likely that such processes transpired on land within geothermal systems.

“The materials we see today can be found on Earth. Icelandic hot springs display a mixed pH, similar to what we use,” Attwater notes.

“RNA nucleotide triplets convey highly specific functional information in every cell,” remarks Zachary Adam from the University of Wisconsin-Madison. “This research is captivating as it may indicate a purely chemical role (rather than informational) for RNA nucleotide triplets that could predate the emergence of living cells.”