Jernej Ule

A gene needs to express itself in order to contribute to cellular functions. This requires information from the gene to be transcribed from DNA into an RNA molecule. Upon its transcription, each RNA molecule undergoes processing, such as splicing and 3' end processing, and passes through many stages of quality control and regulation. The coordinators of these stages are ribonucleoprotein complexes (RNP), which form when multiple proteins bind to an RNA molecule. 

We develop techniques that integrate biochemistry and computational biology to obtain a comprehensive map of interactions between a specific protein and its RNA partners within our cells. We developed the individual-nucleotide resolution UV crosslinking and immunoprecipitation of protein-RNA complexes (iCLIP), and a related method called hiCLIP, which reveals the higher-order conformation of RNPs. We use these methods in collaboration with the group of Nicholas Luscombe to study how the sequence and structure of RNAs defines the composition and function of RNPs.

Cells can change their gene expression by modulating the composition of RNPs. Moreover, genetic studies have identified mutations that disrupt RNPs, which often cause neurologic diseases, particularly the motor neuron disease, also referred to as amyotrophic lateral sclerosis (ALS). We study this disease in collaboration with the group of Rickie Patani by using induced pluripotent stem cells with specific genetic mutations, and differentiating them into motor neurons. We wish to understand how these mutations affect the assembly of RNPs, thereby initiating the molecular cascade leading to disease.