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Department of Molecular Neuroscience
Structure and function of neuronal protein-RNA complexes
Our group studies how protein-RNA complexes control gene expression in neurons. We study the role of RNA regulation in neuronal differentiation and in motor neuron disease. As our model system, we use motor neurons differentiated from induced pluripotent stem cells from healthy individuals or patients with disease-causing mutations. Since neurons are highly polarized cells, an mRNA passes through multiple cellular compartments and through complex regulatory stages in order to produce the right amount of protein at the right time and at the right location. These stages are controlled by RNA-binding proteins (RBPs) and non-coding RNAs (ncRNAs), which assemble into dynamic protein-RNA complexes on mRNAs. We cross the boundaries of experimental and computational biology by developing techniques employing cellular and molecular biology, high-throughput sequencing and predictive modeling. Thereby, we strive towards a systems biology view of protein-RNA interactions in neurons.
AVAILABLE PROJECTS
· The neuronal functions of low-complexity regions in RNA-binding proteins.
· Translational control during unfolded protein response in neurons.
· The role of 3' UTR variation in the molecular pathogenesis of motor neuron disease.
SELECTED PUBLICATIONS
Cereda M, Pozzoli U, Rot G, Juvan P, Schweitzer A, Clark T, Ule J. (2014) RNAmotifs: prediction of multivalent RNA motifs that control alternative splicing. Genome Biol. Jan 31;15(1):R20.
Zarnack K*, König J*, Tajnik M, Martincorena I, Stévant I, Reyes A, Anders S, Luscombe NM*, Ule J* (2013) Direct competition between hnRNP C and U2AF65 protects the transcriptome from the uncontrolled exonization of Alu elements. Cell, Jan 31;152(3):453-66
Tollervey JR, Wang Z., Hortobágyi T, Witten J., Zarnack K., Kayikci M, Clark TA, Schweitzer AC, Rot G, Curk T, Zupan B, Rogelj B, Shaw CE, Ule J. (2011) Analysis of alternative splicing associated with aging and neurodegeneration in the human brain. Genome Research, Oct;21(10):1572-82.
Tollervey JR*, Curk T*, Rogelj B*, Briese M, Cereda M, Kayikci M, König J, Hortobágyi T, Nishimura AL, Zupunski V, Patani R, Chandran S, Rot G, Zupan B, Shaw CE, Ule J. (2011) Characterizing the RNA targets and position-dependent splicing regulation by TDP-43. Nat Neurosci;14(4):452-8.
More: http://www.ulelab.info