Study identifies "RNA dicing" as a key cancer driver

Scientists have uncovered an unexpected way cells can generate cancer-driving proteins - by cutting RNA into shorter, functional fragments rather than following the standard blueprint. This process, newly termed as "RNA dicing," enables the production of a truncated form of the JAK1 protein that remains highly active and can promote tumor growth, particularly when normal gene function is disrupted. The finding challenges conventional views of how genetic information is translated and points to a previously unrecognized mechanism that could influence cancer progression and response to targeted therapies.

The process by which cells turn genes into proteins has long been understood as precise and tightly controlled. But new research shows that cells can unexpectedly cut RNA into shorter fragments that still produce functional proteins, sometimes with harmful consequences.

In a study published in Cell Reports, a team led by Dr. Yuval Malka from Hebrew University together with Dr. William Faller from the University of Bristol, describe a previously underappreciated mechanism they call "RNA dicing," a process that slices RNA molecules into shorter fragments that can still produce functional and potentially harmful proteins.

Their focus: a gene called JAK1, long known to play a central role in regulating how cells grow, divide, and respond to immune signals. When JAK1 functions normally, it helps maintain balance. But when it goes awry, it can fuel cancer.

What the team discovered is that JAK1 doesn't just produce one protein, as was previously assumed. Instead, its RNA can be "diced" into a shorter form that generates a stripped-down but still active protein fragment, essentially the engine of the molecule, known as the JH1 kinase domain.

This truncated version operates differently from its full-length counterpart and can push cells toward uncontrolled growth.

"We're seeing that the cell's protein-making machinery is far more flexible and dynamic than we thought," the researchers suggest. "RNA isn't just a passive messenger. It can be reshaped in ways that change what proteins are made and how they behave."

The implications for cancer are significant.

The study found that the balance between the full-length JAK1 protein and its diced version can influence whether cells remain under control or become tumorigenic. In particular, certain mutations called nonsense mutations, appear to tilt the balance. These mutations disable the normal, tumor-suppressing form of JAK1 while amplifying the activity of the shorter, cancer-promoting version.

In endometrial cancers, this imbalance may help explain why some tumors behave more aggressively.

But the findings also point to an opportunity.

Patients whose tumors carry these mutations, and therefore rely more heavily on the diced JAK1 form, may be especially sensitive to momelotinib, a drug that targets JAK1 activity. In other words, the very mechanism that helps drive the cancer could also expose a vulnerability.

That opens the door to more precise treatment strategies, where patients are matched to therapies based not just on which genes are mutated, but on how those genes are being processed at the RNA level.

Beyond JAK1, this discovery points to a broader shift in how scientists understand gene expression. For decades, the number of proteins a cell could produce was thought to be limited by its genes, but mechanisms like RNA dicing suggest that the proteome is far more expansive and dynamic. This insight also helps address one of the most puzzling questions in cancer research: how the same gene can play opposite roles in disease. In some contexts, a gene acts as a tumor suppressor, while in others it promotes tumor growth as an oncogene. RNA dicing reveals a key step in this process, showing how a single mRNA can be processed in different ways, altering its translation and potentially shifting its function from protective to harmful.

Importantly, these insights are already beginning to translate beyond the lab. The findings have supported the filing of a patent for a novel therapeutic approach based on RNA dicing, and have led to the establishment of a biotech company that has secured initial funding and is advancing toward preclinical trials.

"This adds a new layer to the complexity of biology," the study concludes. "RNA processing itself can generate entirely new functional proteins, with real consequences for disease."

As researchers continue to uncover this previously hidden layer of gene regulation, it is becoming increasingly clear that the mechanisms governing how cells interpret genetic information are far more complex than once believed. In cancer, these newly recognized processes may play a decisive role in shaping disease behavior and in guiding more precise, effective therapeutic strategies.