Researchers at A*STAR Genome Institute of Singapore (A*STAR GIS) have developed a new method called ‘sm-PORE-cupine’ to study individual RNA molecules and reveal how their structure influences gene regulation, a fundamental process that influences cell function in health and disease.
RNA is best known for carrying genetic instructions from DNA to make proteins. But RNA does more than just function as a messenger. Like a thread that can bend, fold, and interact with other molecules, RNA can assume different shapes that influence its behavior inside the cell. These shapes can influence the efficiency of protein production, the duration of RNA molecules, and the progression of diseases such as viral infections.
Because RNA is so flexible and dynamic, it has been difficult to study these structures in detail until now. Most existing methods only provide average images across many RNA molecules, making it difficult to see how individual RNA molecules fold differently, even if they come from the same gene.
Read RNA one molecule at a time
To address this challenge, the A*STAR GIS team developed a new technology called sm-PORE-cupine. This technique combines chemical labels and direct RNA sequencing to detect changes in RNA structure.
This technique uses optimized compounds to mark unpaired RNA bases, which are the more exposed parts of the molecule. These marks act like guideposts, giving researchers clues about how the RNA folds. Nanopore direct RNA sequencing then reads the full-length RNA molecule, allowing scientists to study its structure in more detail.
By applying advanced computational analysis, the team was able to interpret these signals at single-molecule resolution, which helped them see how RNA from the same gene folds and behaves differently.
Linking RNA structure and cell behavior
Using sm-PORE-cupine, the researchers observed that RNA molecules can adopt different structures and that these differences are related to the efficiency of protein production and the rate of RNA degradation.
This is important because protein production and RNA stability are important parts of gene regulation. If these processes go awry, they can cause disease. By giving scientists a clearer picture of how individual RNA molecules behave, this new method provides deeper insight into how RNA structure influences cellular function.
Opening new avenues for disease research and drug discovery
This study also provides new insights into how RNA structure influences viral function and gene regulation in pathogens, including viruses such as SARS-CoV-2.
These findings may help researchers identify new RNA-based therapeutic targets and support the development of antiviral drugs, antifungal treatments, and RNA-targeted therapies. In the long term, the technology and knowledge generated could contribute to better disease diagnosis, drug discovery, and precision medicine by helping scientists better understand how RNA structure influences health and disease.
At A*STAR GIS, we pursue deep scientific understanding to enable better solutions to health and disease. By revealing how RNA molecules adopt different structures and how those structures influence gene regulation, this research lays the foundation for more precise approaches to diagnosis and therapy. ”
Dr. Wan Yue, A*STAR GIS Executive Director
“By leveraging direct RNA sequencing using nanopores, we have a unique ability to study the dynamics of how RNA changes shape,” said co-lead author Dr. Niranjan Nagarajan, Associate Director of AI and Computing at A*STAR GIS and Senior Group Leader in the Metagenomics and Microbial Systems Laboratory. It builds on the great strengths of GIS,” he added. analysis. ”
Their works have recently nature method.
sauce:
Singapore Agency for Science, Technology and Research (A*STAR)
Reference magazines:
Wang, J. others. (2026) Direct RNA sequencing and signal alignment reveals RNA structural ensembles within eukaryotic cells. nature method. DOI: 10.1038/s41592-026-03069-y. https://www.nature.com/articles/s41592-026-03069-y.
