Researchers from the ASTAR Genome Institute of Singapore (ASTAR GIS) have developed a method called sm-PORE-cupine that analyzes individual RNA molecules and their structural influence on gene regulation. The research was published in Nature Methods.
Method
sm-PORE-cupine combines chemical labeling with direct RNA sequencing using nanopores. Optimized chemical compounds mark non-paired RNA bases, which are then detected by nanopore direct RNA sequencing of full-length RNA molecules. Computational analysis interprets these signals at single-molecule resolution.
Previously available methods provided an averaged view across many RNA molecules, which obscured differences in folding among individual RNA molecules from the same gene.
Findings
Using sm-PORE-cupine, researchers observed that RNA molecules from the same gene can adopt different structures. These structural variations were linked to protein production efficiency and RNA degradation rates. Protein production and RNA stability are aspects of gene regulation.
Applications
The study provided insights into RNA structures in viruses such as SARS-CoV-2 and gene regulation in pathogenic organisms. The technology may support:
- Identification of RNA-based therapeutic targets
- Development of antiviral drugs
- Antifungal treatments
- RNA-targeted therapies
Long-term potential applications include disease diagnostics, drug discovery, and precision medicine.
Statements
Dr Wan Yue, Executive Director at A*STAR GIS and lead author, stated that the work uncovers how RNA structures influence gene regulation, providing a foundation for more precise diagnosis and treatment.
Dr Niranjan Nagarajan, co-lead author and Associate Director at ASTAR GIS, noted that leveraging direct RNA sequencing enables study of RNA shape-shift dynamics and builds on ASTAR GIS' capabilities in nanopore sequencing-based analytics.