Szostak Lab Learns the Dance of RNA Replication Process
In the expansive quest to understand life's beginnings, the Jack Szostak Lab is at the forefront of unravelling the origins of life. At the heart of Lab’s ongoing research lies the RNA world hypothesis, which posits that life on Earth initially revolved around RNA molecules before the advent of complex cellular structures.
Now, a recent publication by Szostak lab in Nucleic Acid Research marks a significant milestone in our understanding of RNA replication processes and adds to our knowledge of how genetic information is copied and regulated, paving the way for exciting discoveries and applications in the field of genetics and molecular biology.
RNA, or ribonucleic acid, is like a molecular messenger in our cells. It carries important instructions for making proteins, which are essential for our body's structure and function.
"We think that everything began just from RNA molecules because they [GU1] have some really important features that we think were good enough to kickstart the whole evolution process and create life," explains Marco Todisco, first author on the paper and a researcher with the Szostak lab.
Their recent publication sheds light on the complex interplay between primers and competing sequences, uncovering a dynamic competition during nucleotide hybridization that influences the accuracy of RNA replication processes.
Nucleotide hybridization is like a puzzle game where pieces fit together based on their shapes and patterns. In biology, nucleotides are the building blocks of DNA and RNA, and have specific shapes that allow them to pair up with each other in a particular way. This pairing is called hybridization.
Using complex mixtures of nucleotide sequences, Todisco says the group have been trying to understand what happens when you gradually increase the complexity.
In their study, Todisco explains that RNA molecules follow similar rules to DNA but with their own distinct interactions. To illustrate his point, he describes how gene regulation and prebiotic preservation of genetic information are akin to a metaphorical dance party, where RNA molecules function as dancers seeking their partners (templates). The competition between primers (preferred partners) and competitors (less preferred partners) can lead to transient states akin to mistaken dance partners, ultimately affecting genetic fidelity.
“So instead of just saying a primer is going to bind on the template, I try to understand how this happens, how much time it takes for the primer to go to the template, and how much time it spends there before just falling off by chance,” says Todisco. “What made the difference here is that we find that the competitor is pretty much as good as the primer to find and dance with the template.”
Their findings challenge conventional equilibrium descriptions of RNA interactions. Contrary to previous assumptions, competitors—RNA sequences that can bind to templates but with defects—are not as negligible as once thought. Dr. Todisco’s work highlights how these competitors, while quick to bind and reject, can create transient states where erroneous RNA copies are formed, potentially impacting genetic information preservation.
Moreover, the publication challenges the notion that mutations are the sole contributors to genetic errors. Even with perfect replication fidelity, competition-induced errors can compromise genetic information, suggesting a more nuanced understanding of how genetic information is preserved and regulated.
“It's important that it is not something special about the competitor, it's something special about the matching between sequences,” said Todisco.
Getting at the origins of life can seem an impossible task, but understanding RNA dynamics isn't just about lab experiments.
With potential applications in gene regulation and prebiotic preservation of genetic information, by uncovering the complexities of RNA interactions Todisco and the Szostak Lab’s research contributes to a deeper comprehension of life's origins and evolutionary processes, while raising intriguing questions about the mechanisms that govern genetic stability.