Miha Modic:Decoding core RNA features and spatial organisation of RNP condensation

Publish Date:07.November 2025     Visted: Times       

Title:    Decoding core RNA features and spatial organisation of RNP condensation

Time:    2025-11-12 10:00

Lecturer:  Prof. Miha Modic

Karlsruhe Institute of Technology

Venue:    Room 202, Lu-Jiaxi Building


Abstract

Complex RNA–protein networks play a pivotal role in the formation of many types of biomolecular condensates. How intrinsic RNA features contribute to condensate formation however remains unclear. We developed an integrated transcriptomics framework coupled with an explainable deep learning model to identify a distinct class of condensation-prone RNAs, termed smOOPs (semi-extractable, orthogonal organic phase separation-enriched RNAs). These transcripts are localised to larger intracellular foci, form dense RNA-RNA interaction subnetworks and are heavily bound by RBPs. Intriguingly, they disproportionately encode proteins enriched in intrinsically disordered regions, highlighting an interplay between RNA- and protein-based features of phase separation (Klobucar et al., 2025). To mechanistically resolve how such RNAs scaffold their local microenvironments, we developed HCR-Proxy, a proximity labelling technique coupling Hybridization Chain Reaction (HCR)-based signal amplification with in situ proximity biotinylation (Proxy), enabling proteomic profiling of RNA-proximal proteomes at nanoscale resolution. Benchmarking on nascent pre-rRNAs, HCR-Proxy revealed spatially-resolved maps of RNA interactomes within the nucleolus, and when integrated with deep learning, uncovered a sequence-encoded basis for protein partitioning across nested condensate subcompartments (Trupej et al. 2025). Together, these approaches establish features of condensation-prone RNAs and scalable platform for spatially resolved RNA interactome discovery to dissect RNA-driven condensation principles in native cellular environments..

Bio of the Lecturer

Miha Modic studied biotechnology in Ljubljana, Munich and Cambridge. In 2017 Miha finished his PhD at Helmholtz Zentrum Munich working at the crosstalk between RNA biochemistry and developmental biology. Miha in 2018 pursued his postdoc at The Francis Crick Institute under the mentorship of Jernej Ule. Upon receiving the postdoc-to-PI Wellcome Trust ECR fellowship in 2020, Miha Modic was initially a Sir Henry Wellcome Senior Fellow in the Ule lab and in 2023 started his independent research group as King's Prize Fellow spanning between King's College London and the National Institute of Chemistry. In 2025 Miha accepted a call to the Carl Zeiss Center of Synthetic Genomics between Uni Heidelberg, Mainz & KIT, where he is currently a tenure track professor and Head of Department for Genomics and Development at the Zoological institute of the Karlsruhe Institute of Technology.