Jernej Ule

Jernej.ule@kcl.ac.uk

ule_lab

Website

Research Interests

My group studies the importance of RNA networks in coordinating neuronal differentiation and functions, with a focus on the assembly and function of ribonucleoprotein complexes (RNPs) and their deregulation in amyotrophic lateral sclerosis (ALS). In recent years, we developed new transcriptome-wide methods such as iCLIP to address the mechanisms controlling alternative splicing and localization of RNAs in neurons, to characterize the function of several RNA-binding proteins implicated in ALS, and to reveal how mutations can modify RNP functions and thereby contribute to disease or evolution. We’re developing new therapeutic approaches for ALS and other neurological diseases based on these insights.

Most significant discovery

We recently showed that TDP-43 condensation is required for its RNA binding specificity and function and explained the features of RNA regions that involve the condensation-dependent binding. We thereby addressed the long-standing question of whether condensation propensity of TDP-43, a central player in ALS and several other neurodegenerative diseases, is required for its RNA binding specificity and function.

Educational Interests

• Homeostasis of condensation-prone proteins in neurodegeneration
• Homeostatic mechanisms meditated by protein-RNA networks
• Integrative studies with transcriptomics, machine learning, proteomics and cell biology

Top 4 Publications

Wilkins et al (2024) Creation of de novo cryptic splicing for ALS and FTD precision medicine, Science
Modic et al (2024) Poised PABP-RNA hubs implement signal-dependent mRNA decay in development, Nature Str Mol Biol
Hallegger et al (2021) TDP-43 condensation properties specify its RNA-binding and regulatory repertoire, Cell
Attig et al (2018) Heteromeric RNP assembly at LINEs controls lineage-specific RNA processing, Cell

Methods / Expertise

• Human induced pluripotent stem cell models of neurodegeneration
• Transcriptomics and proteomics
• iCLIP (protein-RNA interactions)
• Computational modelling of protein-RNA regulation
• RNA/protein co-localisation studies with imaging