JUN 28, 2017 09:00 AM PDT

WEBINAR: Integration of 3´ mRNA-Seq and iCLIP to derive high-resolution RNA maps for the regulation of alternative polyadenylation

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  • Group Leader, The Francis Crick Institute
      Jernej Ule obtained his PhD in Molecular Neuroscience from the Rockefeller University, New York, and started his research group at the MRC Laboratory of Molecular Biology in Cambridge. In 2013, he moved with his group to the Institute of Neurology at University College London, and since 2016 the group is based in the Francis Crick Institute. The group studies how protein-RNA complexes regulate gene expression. His group developed iCLIP, a transcriptome-wide method that identifies protein-RNA and RNA-RNA interactions in living cells with high resolution. This method is employed in combination with molecular, cell and computational biology to study how the structure and dynamics of protein-RNA complexes regulates neuronal differentiation and function, and how their dysfunction contributes to neurodegenerative diseases such as ALS. The group also studies the role of transposable elements and non-canonical splicing events in the evolution of alternative splicing [homepage: www.ulelab.info].
    • Postdoctoral Researcher, Institute of Molecular Life Sciences University of Zurich
        Gregor Rot obtained his Msc in Computer Science from the University of Ljubljana, Slovenia, and his Phd in Bioinformatics from the University of Zurich, Switzerland. Gregor is collaborating with several research groups performing data analysis and developing expressRNA.org, an interactive research platform for the study of post-transcriptional modifications.


      DATE: June 28, 2017
      TIME: 9:00AM PDT, 12:00PM EDT, 6:00PM CEST

      Many RNA binding proteins (RBPs) regulate the selection of alternative polyA sites. To understand their regulatory principles, we developed expressRNA, a web platform encompassing computational tools for integration of the QuantSeq 3´ mRNA-Seq, iCLIP and RNA motif analyses. This reveals at nucleotide resolution the ‘RNA maps’, which demonstrate that RBPs bind to specific positions on pre-mRNAs to regulate the polyA sites. Our RNAmotifs2 software also identifies clustered sequence motifs that mediate the regulation of these sites. We used this approach to show that TDP-43, an RBP involved in several neurodegenerative diseases, binds close to the polyA site to repress, and further downstream to enhance their use. We conclude that TDP 43 directly regulates diverse types of pre-mRNA processing events according to common positional principles.

      Learning Objectives:

      • How to analyse 3´ mRNA-Seq QuantSeq data
      • How to use the expressRNA platform
      • Why is it helpful to derive an RNA map, and what does it show us about regulatory mechanisms?

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