Vienna Research Team Reveals How RNA Molecules Influence the Development of Aggressive Leukemia

14.10.2026: Researchers from the University of Veterinary Medicine Vienna, in collaboration with the CeMM Research Center for Molecular Medicine and St. Anna Children’s Cancer Research Institute, have developed a new analytical method that reveals which RNA molecules are involved in cancer-promoting cellular structures. Using this method, the Vienna-based research team identified the RNA molecule Gas5 as an important regulator of NUP98::KDM5A onco-condensates, which control gene activity in aggressive forms of acute myeloid leukemia (AML). These new insights could provide important starting points for cancer research and improved patient treatment. The study was published in the renowned scientific journal The EMBO Journal.

Aggressive forms of leukemia can be driven by so-called fusion oncoproteins. These proteins can accumulate within cells in biomolecular condensates – dynamic, membrane-less structures in which different biomolecules interact to influence gene activity. However, which RNA molecules are involved in these “onco-condensates” has so far remained largely unknown.

“With the method we have developed, called bicon-seq, we can now systematically identify which RNAs are associated with biomolecular condensates. This makes a previously difficult-to-access level of gene regulation measurable,” explains Florian Grebien, senior author of the study and Head of the Unit of Medical Biochemistry at Vetmeduni.

Research Focus: RNA as a Component of Onco-Condensates

The current study focused on the fusion oncoprotein NUP98::KDM5A. This protein occurs in aggressive forms of AML and promotes the formation of condensates in leukemia cells, which are required for the activation of leukemia-related genes.

The new analytical method, bicon-seq, provides quantitative information on the cellular solubility of RNA molecules. According to the researchers, changes in this parameter indicate whether an RNA molecule is more or less strongly associated with biomolecular condensates.

“What is particularly relevant is that this approach does not just provide us with a snapshot. We can track how the RNA composition of condensates changes when key components are specifically disrupted or degraded,” says Melanie Allram, first author of the study.

The lncRNA Gas5 Plays a Central Role in the Proliferation of Leukemia Cells

The analyses identified several long non-coding RNAs (lncRNAs) associated with NUP98::KDM5A onco-condensates. One lncRNA in particular stood out: Gas5. This RNA was highly expressed in AML cells, co-localized with NUP98::KDM5A in condensates, and proved to be important for the proliferation of leukemia cells.

When Gas5 was specifically downregulated using CRISPRi – a method for selectively suppressing gene expression – the gene activity of AML cells changed significantly. Among the affected genes were those involved in cell differentiation and programmed cell death.

“This shows that the Gas5 lncRNA is not only a component of the condensates but can also influence their function,” emphasizes Melanie Allram.

A New Method for Investigating the RNA Biology of Condensates

The study describes a new experimental approach for investigating biomolecular condensates.

Florian Grebien explains: “bicon-seq makes it possible to quantitatively determine the RNA composition of these structures under normal and disrupted conditions. This opens up new opportunities to investigate the role of RNAs in regulating disease-relevant condensates.”

The findings highlight the importance of non-coding RNAs for the function of fusion oncoproteins. According to the researchers from the Grebien Lab, further investigations will aim to clarify in greater detail how the interaction between Gas5 and the NUP98::KDM5A fusion protein influences gene activity and leukemia development.

Publication

The study “Uncovering essential RNA components of fusion oncoprotein condensates using bicon-seq” by Melanie Allram, Thomas Eder, Pablo Fernandez-Pernas, Laura Quell, Núria Lupión-Garcia, Raj Bhayadia, Bruno Di Stefano and Florian Grebien was published in The EMBO Journal.