Three graduate students, namely Noreen Ahmed, Nadine Ahmed, and Didier Bilodeau, led by Professor John Pezacki, who chairs the Department of Chemistry and Biomolecular Sciences, have successfully engineered a ground-breaking enzyme that can specifically cut small, non-coding RNAs. No enzyme has been found in nature that can perform this function.
This new enzyme could be a powerful tool for studying these important RNA species and could also be used to target non-coding RNAs that are associated with disease.
“This study aimed to engineer an enzyme capable of specifically degrading small, non-coding RNAs, thereby shedding light on their functions and paving the way for potential therapeutic applications,” explains Professor Pezacki.
“All life on earth uses the same 20 amino acids to make proteins. Thanks to genetic code expansion, we can introduce a 21st amino acid and engineer new functions relatively easily”
John Pezacki
— Full Professor & Chair of the Department of Chemistry and Biomolecular Sciences
The research, which took place over the past three years, was carried out in the Centre for Chemical and Synthetic Biology, where the researchers could rely on state-of-the-art tools and technologies.
“All life on earth uses the same 20 amino acids to make proteins. Thanks to genetic code expansion, we can introduce a 21st amino acid and engineer new functions relatively easily. We can then take advantage of the known qualities of existing proteins and add new functionality, in this case catalysis, to a protein that inherently shows no catalytic activity,” added Professor Pezacki.
The modified enzyme degraded microRNA-122 with surprising efficiency, effectively blocking its function as a crucial host factor for HCV replication. This ground-breaking finding has important ramifications for antiviral therapies because it suggests a way to target host elements that are crucial for virus replication.
The new enzyme also serves as an effective tool for studying small, non-coding RNAs, allowing researchers to gain deeper insights into their functions and potential implications in various human diseases.
The ability to engineer an enzyme with catalytic activity to prompt the degradation of small non-coding RNAs represents a milestone in the field of biotechnology. By introducing a 21st amino acid and harnessing the inherent qualities of existing proteins, uOttawa’s researchers at the Pezacki Lab have expanded the repertoire of enzymatic functions beyond those of the 20 canonical amino acids. This development not only provides a valuable tool for studying non-coding RNAs, but also opens new avenues to create new biocatalysts capable of targeting disease-associated RNA species.
The study “An unnatural enzyme with endonuclease activity towards small non-coding RNAs” was published in Nature Communications on June 24, 2023.