RNA-based life's genome repair origins: A fascinating journey into the origins of life
The question of which came first, DNA or proteins, has long been a topic of debate among scientists. But a new study by Saurja DasGupta, a biochemist at the University of Notre Dame, offers a compelling alternative hypothesis: RNA-based life. The research, published in Nature Communications, presents a key mechanism for sustaining RNA-based life: an engineered enzyme that selectively recognizes and repairs broken RNA.
In most modern cells, DNA stores the genetic blueprint, and proteins are responsible for replicating, repairing, and building from those blueprints. However, proteins require instructions from DNA to be made in the first place, creating a chicken-and-egg dilemma. DasGupta's research suggests that RNA, with its dual storage and catalysis capabilities, could have been the solution to this problem.
The RNA-based enzyme, or ribozyme, engineered by DasGupta and colleagues, targets a distinguishing feature of broken RNA: a phosphate group at the end of the broken RNA chain. This enzyme selectively recognizes and repairs broken RNA, while ignoring intact strands that terminate in a hydroxyl group. This mechanism could have been crucial for primordial RNA repair, ensuring that genetic information was preserved and passed on to future generations.
The RNA World hypothesis, which posits that the earliest forms of life on Earth were powered exclusively by RNA, is supported by this research. RNA molecules, which preceded DNA and proteins, could have encoded genes and facilitated cellular processes. The study highlights the importance of RNA repair mechanisms in early life forms, as the lack of such mechanisms would have led to the permanent loss of genetic information, effectively stopping life in its tracks.
However, the study of primordial RNA systems is challenging, as these systems no longer exist. Researchers must engineer new ribozymes through in vitro evolution, a process that involves selecting RNA catalysts with specific properties from trillions of RNA molecules inside test tubes. This process is often a matter of luck, and researchers must be prepared to start over if they don't get the desired results.
DasGupta's research group initially set out to tweak the biochemistry of an existing class of ribozymes, but they encountered unexpected results. Instead of discarding these results, they followed up on them and uncovered a brand-new ribozyme. This unexpected finding has significant implications for our understanding of the origins of life and has also provided a potential solution to a major challenge in biotechnology.
Broken RNA is common in viral infections and is a sign of abnormal cell function in certain cancers. Standard RNA sequencing techniques, which are used to analyze the genetic markers of these diseases, miss out on broken RNA, as the chemical tags that mark RNA strands for analysis are not designed to attach to broken ends. The newly-engineered ribozyme, which is selective for broken RNA, could be used to render cleaved strands visible by isolating them for special preparation prior to RNA sequencing.
The study's collaborators, Annyesha Biswas and Zoe Weiss, played a crucial role in the research. Biswas, a postdoctoral researcher in the Department of Chemistry and Biochemistry, was supported by the University's Bioengineering and Life Sciences initiative. Weiss, an M.D.-Ph.D. student at the Massachusetts Institute of Technology and Harvard University, also contributed to the study.
In conclusion, the study of RNA-based life's genome repair origins is a fascinating journey into the origins of life. The research highlights the importance of RNA repair mechanisms in early life forms and provides a potential solution to a major challenge in biotechnology. As DasGupta and her colleagues continue to explore these new frontiers in ancient RNA biology and modern diagnostics, we can expect to uncover more fascinating insights into the origins of life and the potential of RNA-based systems.
