Variation is where the story lives
In Singapore, researchers at A*STAR's Genome Institute have developed a method to read RNA molecules one at a time, revealing how their folded shapes govern the most fundamental processes of gene regulation. Where science once averaged the behavior of millions of molecules together, sm-PORE-cupine now distinguishes the individual from the crowd — exposing structural variations that may explain why disease takes hold in some and not others. It is less a single discovery than a new instrument placed in the hands of those who study life at its most elemental level.
- For decades, RNA has been studied in bulk, obscuring the molecular-level variation that may be the hidden engine of disease — that blind spot is now closing.
- The method combines chemical labeling with nanopore sequencing to map the precise folds of individual RNA molecules, revealing differences invisible to population-level analysis.
- These structural variations are not noise: they directly control how efficiently RNA is translated into protein and how long it survives in the cell — two processes central to health and illness.
- Early findings have already illuminated how RNA structure shapes viral behavior in pathogens like SARS-CoV-2, pointing toward new targets for antiviral and RNA-based therapies.
- The A*STAR team positions sm-PORE-cupine not as a final answer but as a foundational capability — one that makes possible questions about disease, diagnosis, and precision medicine that could not previously be asked.
In a Singapore laboratory, researchers have developed a way to read RNA molecules one at a time — and what they are finding is quietly reshaping how scientists understand disease. The method, called sm-PORE-cupine, comes from A*STAR's Genome Institute and allows researchers to observe how individual RNA molecules fold and shift in ways that were previously invisible.
RNA is commonly described as a messenger carrying genetic instructions from DNA to the protein-building machinery of the cell. But that description understates its complexity. RNA is more like a string that bends and twists into countless shapes, and those shapes carry consequence. The way a molecule folds affects how quickly it becomes protein, how long it survives, and even how viruses like SARS-CoV-2 behave inside a host. Until now, scientists have mostly studied RNA in bulk — averaging millions of molecules at once — a method that works for broad questions but erases the variation between individuals.
Sm-PORE-cupine works by chemically marking the exposed, unfolded regions of an RNA molecule, then using nanopore sequencing to read it from end to end. Computational analysis interprets these signals at the single-molecule level, showing precisely how one RNA differs from another even when their sequences are identical. What the team found is that these structural differences are not random: they directly govern how efficiently RNA is translated into protein and how quickly the cell degrades it — processes fundamental to gene regulation and, when disrupted, to disease.
The method has already yielded new insights into viral RNA structure, with implications for antiviral and antifungal drug development. Lead researcher Dr. Wan Yue described the work as foundational, while colleague Dr. Niranjan Nagarajan highlighted the team's new capacity to watch RNA change shape in real time. The deeper promise is a medicine tailored not just to a person's genetic sequence, but to how those genes actually behave — molecule by molecule — inside living cells.
In a laboratory in Singapore, researchers have figured out how to read RNA molecules one at a time—and what they're finding is changing how scientists think about disease. The breakthrough comes from A*STAR Genome Institute of Singapore, where a team has developed a method called sm-PORE-cupine that lets them watch individual RNA molecules fold and shift in ways that were invisible before.
RNA is often described as a messenger, ferrying genetic instructions from DNA to build proteins. But that description misses something crucial. RNA is not a rigid instruction manual. It's more like a string that can bend and twist into countless shapes, and those shapes matter enormously. The way an RNA molecule folds affects how quickly cells can turn it into protein, how long the molecule survives in the cell, and even how viruses like SARS-CoV-2 behave once they infect a host. Until now, scientists have mostly studied RNA in bulk—averaging the behavior of millions of molecules at once. That approach works for some questions, but it obscures the variation that exists between individual molecules, even when they come from the same gene.
The new method works by chemically marking the parts of an RNA molecule that are exposed and unfolded, then using nanopore sequencing to read the entire molecule from end to end. Think of the chemical marks as signposts that reveal the shape of the RNA as it actually exists. Advanced computational analysis then interprets these signals at the level of single molecules, showing researchers exactly how one RNA differs from another, even when they're identical in sequence.
What the A*STAR team discovered is that these structural differences are not random noise. They found that the way an RNA folds directly influences how efficiently it gets translated into protein and how quickly the cell breaks it down. These are not minor details. Protein production and RNA stability are fundamental to how genes are regulated, and when those processes malfunction, disease often follows. By revealing the structural basis for these variations, sm-PORE-cupine gives researchers a window into why some cells behave differently from others, and why some people get sick while others don't.
The implications ripple outward quickly. The method has already provided new insights into how RNA structures affect viral function, particularly in pathogens like SARS-CoV-2. That knowledge could help researchers identify new targets for antiviral drugs, antifungal treatments, and RNA-based therapies that don't yet exist. Dr. Wan Yue, the executive director of A*STAR GIS and lead author of the work, framed it as foundational: the method lays groundwork for more precise diagnosis and treatment. His colleague Dr. Niranjan Nagarajan emphasized that the team now has a unique capability to watch how RNA molecules change shape in real time, building on Singapore's existing strengths in nanopore sequencing technology.
What makes this moment significant is not that one mystery has been solved, but that a new tool has been placed in researchers' hands. The ability to read individual RNA molecules opens questions that couldn't be asked before. It creates the possibility of understanding disease not as a simple malfunction, but as a breakdown in the intricate choreography of molecular folding and unfolding. In the longer term, that understanding could reshape how drugs are discovered, how diseases are diagnosed, and how medicine becomes truly personalized—tailored not just to a person's genes, but to how those genes actually behave inside their cells.
Citações Notáveis
By uncovering how RNA molecules adopt different structures and how these structures influence gene regulation, this work lays the foundation for more precise approaches to diagnosis and treatment.— Dr. Wan Yue, Executive Director, A*STAR Genome Institute of Singapore
By leveraging direct RNA sequencing using nanopores, we now have a unique capability to study the dynamics of how RNAs shape-shift.— Dr. Niranjan Nagarajan, Associate Director, A*STAR GIS
A Conversa do Hearth Outra perspectiva sobre a história
Why does it matter that we can now read individual RNA molecules instead of averaging across millions?
Because variation is where the story lives. Two RNA molecules with identical sequences can fold completely differently, and that difference changes everything—how much protein gets made, how long the molecule lasts. We were missing that before.
So this isn't just about seeing more detail. It's about seeing a different kind of detail entirely.
Exactly. We were looking at the average behavior of a crowd. Now we can watch individual people in that crowd and see they're not all doing the same thing.
And that matters for disease because...
Because disease is often about things going wrong at that individual level. A virus might exploit a particular RNA fold. A cancer cell might have RNA that folds in a way that produces too much of a growth protein. If you only see the average, you miss the mechanism.
What about the practical side—drug discovery?
This gives you new targets to aim at. Instead of trying to block a protein after it's made, you might be able to target the RNA structure itself, prevent it from folding in the way that causes disease. That's a whole new category of drugs.
Is this ready to change medicine tomorrow?
No. This is foundational work. It's the tool that lets the next generation of questions get asked. But tools like this—they tend to accelerate everything that comes after.