Integrative profiling of condensation-prone RNAs
Inside every cell, RNAs and proteins constantly interact. They form tiny, liquid-like droplets called biomolecular condensates, which are essential for organising cellular life. Yet, we do not fully understand why some RNAs tend to cluster together more than others. In this interdisciplinary study, researchers from the National Institute of Chemistry (Tajda Klobučar, Jona Novljan, Jernej Ule, Miha Modic), The Francis Crick Institute and Jožef Stefan Institute combined several experimental approaches to identify a new class of condensation-prone RNAs during early development, which they named smOOPs (semi-extractable and orthogonal organic phase separation-enriched RNAs).
These RNAs are unusually “sticky”: they resist standard RNA extraction methods and are heavily bound by RNA-binding proteins. Moreover, researchers observed that smOOPs gather in visible foci and are more interconnected than expected, demonstrating that they naturally prefer to colocalise/condense inside cells. Using deep learning, they found that smOOPs share distinctive features: they are long transcripts with lower sequence complexity, strong internal folding, and characteristic protein-binding patterns. Remarkably, the proteins encoded by these RNAs also tend to contain long, flexible segments known as intrinsically disordered regions, which themselves promote condensation. This indicates an intriguing interplay between RNA- and protein-based features in phase separation.
The discovery of smOOPs not only expands our understanding of condensation-prone RNAs, but also demonstrates how combining biochemical experiments with deep learning can reveal the hidden logic of life’s molecular networks.
Link: https://www.cell.com/cell-genomics/fulltext/S2666-979X(25)00321-0
Contact for more info: miha.modic(at)ki.si