Inside the intricate world of cellular biology, researchers have made a groundbreaking discovery that unveils the mysteries of cellular organization. Scientists at the Karlsruhe Institute of Technology (KIT) have identified a new class of RNA, termed smOOPs, which plays a crucial role in the formation of biomolecular condensates. These findings, published in the journal Cell Genomics, could have significant implications for understanding developmental defects, cancer, and neurodegenerative diseases.
Biomolecular condensates, the liquid-like droplets formed by RNAs and proteins, are essential for organizing cellular life. However, the reason why some RNAs cluster more readily than others has remained elusive until now. The study conducted by KIT, in collaboration with the National Institute of Chemistry in Slovenia and The Francis Crick Institute, combines experimental analyses with deep learning to reveal these hidden dynamics.
Understanding Biomolecular Condensates
Within human cells, biological condensates act as organizational hubs, supporting a wide range of cellular functions from gene regulation to stress responses. Professor Miha Modic from the Zoological Institute at KIT explains, “These biological condensates are accumulations that arise through phase separation, a process in which molecules segregate from their surroundings – much like how oil separates from water.” In cells, this process causes RNA and proteins to form distinct, membrane-less droplets.
The discovery of smOOPs, which stands for semi-extractable and orthogonal organic phase separation-enriched RNAs, marks a significant advancement in understanding how these condensates form. The study highlights the role of smOOPs during early development, where they exhibit unique properties that influence cellular organization.
Sticky RNAs and Cellular Organization
Professor Modic elaborates, “During early development, each cell state expresses a distinct set of condensation-prone RNAs. These RNAs ‘tune’ or scaffold the phase-separation landscape of that cell. We have discovered that smOOPs are unusually ‘sticky’, highly cell-type specific, and are present during early development.” These RNAs resist standard extraction methods and are heavily bound by RNA-binding proteins, indicating their significant role in cellular processes.
Furthermore, researchers observed that smOOPs naturally prefer to condense inside cells, forming visible clusters that are more interconnected than previously expected. Using deep learning, the team identified distinctive features of smOOPs, including long transcripts with lower sequence complexity, strong internal folding, and characteristic protein-binding patterns.
“The discovery of smOOPs not only expands our understanding of condensation-prone RNAs but also demonstrates how combining biochemical experiments with deep machine learning can reveal the hidden logic of life’s molecular networks,” says Modic.
Implications for Future Research
Investigating how cells maintain their internal organization is crucial for understanding our biology. Modic explains, “Both RNA and protein contribute to condensate formation. That coupling becomes particularly relevant in development. When this machinery malfunctions, it causes diseases.” By identifying smOOPs and their RNA-RNA interaction network, researchers now have a conceptual and mechanistic framework to interpret pathogenic condensates in disease.
This discovery opens new avenues for research into how disruptions in condensate formation are linked to various diseases. The findings could lead to novel therapeutic strategies targeting these molecular networks, potentially offering new hope for patients with developmental disorders, cancer, and neurodegenerative conditions.
Looking Ahead
The research conducted by KIT and its collaborators represents a significant step forward in our understanding of cellular organization. As scientists continue to explore the role of smOOPs and other condensation-prone RNAs, the potential for new insights into cellular function and disease mechanisms grows.
The study, titled “Integrative profiling of condensation-prone RNAs during early development,” provides a foundation for future investigations into the complex interplay between RNA and protein in cellular processes. As the scientific community delves deeper into these findings, the hope is that this knowledge will lead to innovative approaches for diagnosing and treating diseases linked to cellular disorganization.
Original publication: Klobučar, T., Novljan, J., Iosub, I. A., Kokot, B., Urbančič, I., Jones, D. M., Chakrabarti, A. M., Luscombe, N. M., Ule, J., Modic, M.: Integrative profiling of condensation-prone RNAs during early development. Cell Genomics. DOI: 10.1016/j.xgen.2025.101065
