- starks@ inf.ethz.ch
- +41 44 632 23 74
Department of Computer Science
Biomedical Informatics Group Universitätsstrasse 6
- CAB F52.1
I am a Masters student in Computer Science and research assistant in the Biomedical Informatics Group.
In 2014 I received my Bachelor’s degree in mathematics from New York University and joined the lab shortly after while it was located at Memorial Sloan Kettering Cancer Center in New York City. I am broadly interested in modelling large-scale clinical and medical data.
Abstract Precise 5' splice-site recognition is essential for both constitutive and regulated pre-mRNA splicing. The U1 small nuclear ribonucleoprotein particle (snRNP)-specific protein U1C is involved in this first step of spliceosome assembly and important for stabilizing early splicing complexes. We used an embryonically lethal U1C mutant zebrafish, hi1371, to investigate the potential genomewide role of U1C for splicing regulation. U1C mutant embryos contain overall stable, but U1C-deficient U1 snRNPs. Surprisingly, genomewide RNA-Seq analysis of mutant versus wild-type embryos revealed a large set of specific target genes that changed their alternative splicing patterns in the absence of U1C. Injection of ZfU1C cRNA into mutant embryos and in vivo splicing experiments in HeLa cells after siRNA-mediated U1C knockdown confirmed the U1C dependency and specificity, as well as the functional conservation of the effects observed. In addition, sequence motif analysis of the U1C-dependent 5' splice sites uncovered an association with downstream intronic U-rich elements. In sum, our findings provide evidence for a new role of a general snRNP protein, U1C, as a mediator of alternative splicing regulation.
Authors Tanja Dorothe Rosel, Lee Hsueh Hung, Jan Medenbach, Katrin Donde, Stefan Starke, Vladimir Benes, Gunnar Rätsch, Albrecht Bindereif
Submitted The EMBO journal