A remarkably tiny RNA molecule, dubbed QT45, has been discovered by researchers at the MRC Laboratory of Molecular Biology (LMB) in the United Kingdom, capable of copying itself and its complementary strand – a critical step towards understanding self-replication and the origins of life, according to a study published today in the journal Science.
For decades, scientists have theorized that RNA molecules played a central role in the emergence of life on Earth, potentially forming in a “primordial soup” and beginning a process of replication and evolution. However, previous discoveries of RNA strands capable of copying other RNA were hampered by their size and complexity, making self-replication seem improbable. The prevailing assumption was that only large, intricate RNA molecules possessed the necessary capabilities.
The LMB team’s breakthrough challenges this long-held belief. QT45, a short RNA polymerase ribozyme, is significantly smaller than previously identified RNA replicators. This reduced size not only facilitates its ability to copy itself but as well increases the plausibility that such a molecule could have arisen spontaneously in the early stages of life, researchers say.
“This research offers a glimpse into what the earliest steps of life might have looked like and deepens our understanding of the fundamental molecules that underpin all living systems,” explained lead author Edoardo Gianni. “Everyone in this field had been working on the same ribozyme lineage for over 30 years and believed that finding a new one would be very difficult, and that it had to be a long RNA sequence to carry out its function. By identifying a small RNA, it makes the whole idea that self-replicating RNA emerged spontaneously much more likely, and thanks to its size, it managed to copy all of itself and its template – unlike previous work where only small parts were copied.”
The team achieved this discovery by generating extensive pools of random RNA sequences and meticulously selecting those exhibiting RNA-copying activity. Through repeated rounds of laboratory evolution, QT45 emerged as a highly efficient ribozyme, demonstrating its ability to copy diverse RNA sequences and, crucially, to synthesize both itself and its complementary strand.
Researchers have now set their sights on combining the two key reactions QT45 demonstrates – copying itself and its complementary strand – to initiate a continuous self-replication cycle. Gianni added that the discovery also has broader implications for the likelihood of life emerging elsewhere in the universe and the potential for similar processes to occur on other planets.
Dr. Glenn Wells, Deputy Executive Chair at the Medical Research Council (MRC), described the breakthrough as “discovering a piece of the puzzle of how life began on earth!” He highlighted the collaborative nature of the research, noting how it “showcases how our MRC LMB researchers are continually resetting the boundaries, merging physics, chemistry and biology to understand the building blocks of life.”