I’m thrilled to sit down with Ivan Kairatov, a renowned biopharma expert with extensive experience in research and development, and a deep understanding of cutting-edge technologies in the industry. Today, we’re diving into a groundbreaking advancement in mapping RNA-protein interactions—a discovery that could transform our approach to treating complex diseases like cancer and Alzheimer’s. In this conversation, we’ll explore the significance of these cellular interactions, the innovative technology behind mapping them, surprising findings from recent studies, and the potential for new therapeutic strategies.
Can you start by explaining what RNA-protein interactions are and why they’re so critical to how cells function?
Absolutely. RNA-protein interactions are essentially the conversations happening inside our cells between RNA molecules and proteins. RNA, often thought of as a messenger carrying genetic instructions, doesn’t work alone—it partners with proteins to control a wide range of cellular activities. These partnerships are vital for processes like turning genes on or off, repairing damage, and responding to stress. Without these interactions, cells couldn’t adapt to changes or maintain their functions, which would disrupt everything from growth to immune defense. They’re foundational to life at the cellular level.
What specific roles do these interactions play in areas like gene regulation or how cells handle stress?
In gene regulation, RNA-protein interactions are like the dimmer switches of a cell. They determine when and how much a gene is expressed by controlling how RNA is processed or translated into proteins. For stress response, these interactions help cells react to threats—like heat, toxins, or lack of nutrients—by quickly adjusting which proteins are made to protect or repair the cell. For example, certain proteins bind to RNA to prioritize the production of stress-response molecules, ensuring the cell survives tough conditions. It’s a dynamic system of checks and balances.
Why has it been so challenging for scientists to study these interactions until recently?
Historically, the challenge has been the sheer complexity and fleeting nature of these interactions. RNAs and proteins often bind briefly and in tiny amounts, making them hard to capture. Older methods could only look at small subsets of interactions, often focusing on well-known pairs, which meant we missed the bigger picture. Plus, the tools weren’t sensitive enough to detect these subtle, transient connections without disrupting the cell’s natural state. It’s like trying to photograph a fast-moving dance in the dark—we just didn’t have the right camera until now.
Your team has developed a new technology to map these interactions. Can you walk us through how it works in simple terms?
Sure, think of our technology as a way to take a snapshot of a cell’s conversations. We essentially freeze the moment when RNAs and proteins are physically touching inside the cell. We tag the proteins and chemically link them to the RNAs they’re bound to, preserving that interaction. Then, we convert these pairs into unique DNA barcodes—kind of like labeling each conversation with a readable ID. These barcodes are run through standard sequencing machines, giving us a complete catalog of who’s talking to whom in the cell. It’s a game-changer because it’s comprehensive and unbiased.
What makes this method stand out compared to older approaches for studying RNA-protein connections?
The biggest difference is the scale and precision. Older methods were like fishing with a small net—you’d catch a few known interactions, but miss most of the ocean. Our approach maps hundreds of thousands of interactions in one go, including ones no one even suspected. Also, it doesn’t require prior knowledge of what to look for, so we’re not biased toward familiar players. Plus, it gives us detailed info about where exactly on the protein or RNA the interaction happens, which older techniques often couldn’t pinpoint. It’s a whole new level of insight.
Your research uncovered over 350,000 interactions in just two human cell lines. What surprised you most about these findings?
The sheer number was staggering, but what really caught us off guard was how many of these interactions involved proteins we didn’t expect to be RNA-binding. We confirmed the usual suspects, of course, but discovering hundreds of new players was a revelation. It showed us that the network of cellular communication is far more intricate than we imagined. Some of these unexpected proteins are tied to critical functions, and finding them interacting with RNA opens up entirely new questions about their roles in health and disease.
One specific finding was about phosphoglycerate dehydrogenase, or PHGDH, and its link to Alzheimer’s. Can you explain what you discovered about this enzyme?
We found that PHGDH, an enzyme we’ve previously linked to Alzheimer’s as a potential early biomarker, binds to specific messenger RNAs related to cell survival and nerve growth. This was intriguing because it suggests PHGDH isn’t just a metabolic player—it might directly influence how brain cells protect themselves or grow. Since Alzheimer’s involves the loss of nerve function, this interaction could be a piece of the puzzle in understanding how the disease progresses or how we might intervene to support brain health.
How could this discovery around PHGDH lead to better ways to detect or treat Alzheimer’s early on?
If PHGDH’s interactions with these RNAs are indeed tied to neuronal health, we could potentially use its activity or binding patterns as a more precise marker for early Alzheimer’s detection, perhaps through blood tests. For treatment, disrupting or enhancing these specific interactions might offer a way to slow disease progression—say, by protecting nerve growth or boosting cell survival mechanisms. It’s early days, but it points to a targeted approach, which is what we need for such a complex condition.
Another finding was about a long noncoding RNA called LINC00339 and its connection to cancer. Can you break down what this means?
We discovered that LINC00339, a long noncoding RNA, interacts with 15 different membrane proteins. What’s significant is that this RNA is often elevated in several types of cancer. These interactions with membrane proteins—which are involved in cell signaling and structure—might explain how LINC00339 contributes to tumor behavior. It could be influencing how cancer cells communicate, grow, or even spread by tweaking the activity of these proteins at the cell’s surface. It’s a clue to how noncoding RNAs drive disease.
Why is it important to pinpoint specific regions and sequences where RNA and protein interactions occur?
Knowing the exact contact points is like having a blueprint for intervention. If we understand precisely where an RNA binds to a protein, we can design drugs to block or mimic that interaction, depending on whether it’s harmful or beneficial. This level of detail also tells us about the protein’s preferences—why it chooses certain RNAs over others—which helps us predict its behavior in different contexts. For drug development, this precision is invaluable because it reduces guesswork and lets us target therapies right at the source of a problem.
What is your forecast for the future of RNA-protein interaction research and its impact on disease treatment?
I’m incredibly optimistic. With technologies like ours, we’re just scratching the surface of understanding these cellular networks. In the next decade, I expect we’ll map interactions across many more cell types and disease states, revealing key control points for conditions like cancer, neurodegeneration, and even infectious diseases. Therapeutically, I foresee a wave of precision medicines—drugs designed to tweak specific RNA-protein interactions rather than broadly targeting entire pathways. It’s a shift toward truly personalized treatments, and I believe it will redefine how we tackle some of the toughest health challenges out there.
