RNA-based life's genome repair origins: A fascinating insight into the origins of life and a potential breakthrough in biotechnology
The origins of life on Earth have long been a subject of debate and speculation. While DNA is the genetic blueprint of most modern cells, and proteins are responsible for replicating, repairing, and building from those blueprints, the question of which came first remains a mystery. However, a recent study by Saurja DasGupta, a biochemist at the University of Notre Dame, offers a fascinating insight into this age-old question.
DasGupta's research focuses on the structure, function, and evolution of RNA, an intermediary molecule that can both store genetic information and catalyze biochemical reactions. In a study published in Nature Communications, DasGupta and colleagues present a key mechanism for sustaining RNA-based life: an engineered enzyme that selectively recognizes and repairs broken RNA.
The RNA-based enzyme, or ribozyme, engineered by the researchers pastes together pieces of RNA and targets a distinguishing feature of broken RNA: a phosphate group at the end of the broken RNA chain. This enzyme seeks out terminal phosphate groups in RNA, while ignoring strands that end with standard hydroxyl groups, suggesting that it could have been important for primordial RNA repair.
The RNA World hypothesis posits that the earliest forms of life on Earth were powered exclusively by RNA. This hypothesis suggests that RNA molecules preceded DNA and proteins for encoding genes and facilitating cellular processes, respectively. Modern organisms have repair mechanisms to mend broken DNAs, so if early life forms carried their genes in RNA, then a similar repair process must have existed. Otherwise, genetic information would have been permanently lost, effectively stopping life in its tracks.
The study of primordial RNA systems is challenging because they do not exist anymore. Researchers need to engineer new ribozymes through a process called in vitro evolution, which entails selecting RNA catalysts with particular properties from trillions of RNA molecules inside test tubes. While this process often comes down to luck, DasGupta's research group made an unexpected discovery.
Initially, DasGupta's research group set out to tweak the biochemistry of an existing class of ribozymes. However, when they saw unexpected results, they followed those up instead of discarding them, and uncovered something brand new. The existence of this ribozyme has interesting implications for our understanding of the origins of life, and it wasn't found sooner.
Beyond primordial biology, the significance of the newly-engineered ribozyme extends into the realm of biotechnology. Broken RNA is common in viral infections and is a sign of abnormal cell function in certain cancers. Standard RNA sequencing techniques used to analyze the genetic markers of these diseases miss out on broken RNA, since the chemical tags that mark RNA strands for analysis are not designed to attach to broken ends.
The RNA-repair ribozyme is selective for broken RNA, so it could be used to render cleaved strands 'visible' by isolating them for special preparation prior to RNA sequencing. DasGupta's research group is currently optimizing the ribozyme's reaction efficiency while broadening the range of potential molecular targets.
This breakthrough has the potential to revolutionize our understanding of the origins of life and our ability to diagnose and treat diseases. As DasGupta says, 'What began as a quest for insight into the origins of RNA-based life and ended in an unanticipated finding has also provided a potential solution to a major challenge in biotechnology.' The future of biotechnology and our understanding of the origins of life are certainly exciting prospects.
