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PhD Defense: Christian Garde
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2016-02-04: Mechanisms and functions of protein-RNA interactions. The defense will take place Thursday 4 February 2016 at 13:00, Center for Biological Sequence Analysis, DTU, Building 208, auditorium 062

Everybody is welcome. Registration is not necessary.

Assessment committee:

    Professor Ole Winther, DTU (chairman)

    Professor Anders Krogh, Department of Biology, University of Copenhagen

    Associate professor Quaid Morris, Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Canada

Chair of defense:
Associate professor Jose Maria Gonzalez-Izarzugaza, Center for Biological Sequence Analysis, DTU
Supervisors:
Associate professor Christopher Workman, Center for Biological Sequence Analysis, DTU

Abstract:

Protein-RNA interactions are pivotal players in the regulation of gene expression from transcription to translation.  Dysregulation of these interactions has been implicated in various complex diseases, and the interplay between proteins and RNA is still poorly understood.  Further, the discovery of non-coding RNA has added to the complexity of cellular regulation, amd the understanding is hindered since many non-coding RNAs are yet to be discovered and characterized. This thesis aims to identify putative functional non-coding RNA, as well as to develop novel assays and computational tools for characterizing RNA binding proteins, RNAs and their interaction networks.The thesis is divided into two parts.  The first part provides a brief literature review to provide the reader with the necessary background information.  The second part of the thesis presents the achieved scientific results, arranged into four studies. The first study presents a novel assay for proteomewide in vivo characterization of the poly(A) RNA bound proteins. We demonstrate that the precision of our assay is superior to that of the previous gold standard, and identify known as well as putative poly(A) RNA binding proteins. We highlight its application for exploring changes in the poly(A) RNA bound landscape in different tissues and under different conditions. The second study presents an integrated resource of protein-RNA interaction networks named RAIN. We integrate curated interactions,  miRNA target predictions, high-throughput pull down studies, as well as literature text mining to provide a collected overview of protein-RNA interaction networks.   RAIN can  be  queried  for  a  protein  or  RNA  of  interest,  and  provides  the  user  with the associated interaction network. Furthermore, the resource interfaces with STRING to include predicted protein-protein interaction networks as well. The third study presents a computational tool, RRMDecoder, for specificity inference of RNA recognition motif (RRM) containing proteins. RRMDecoder displays superior performance to the Nearest Neighbor approach and RPI-seq and can be applied to characterize RRM proteins across species. The final study presents a computational screen for conserved RNA structures (CRSs) based on structural alignments of vertebrate genomes. We identify thousands of CRSs which are confirmed by genome-wide structure probing and enriched in the binding sites of RNA binding proteins. We confirm the expression of a subset of CRSs in human tissue and demonstrate that human and mouse othologs can adopt similar structure despite low similarity in primary sequence. Collectively, the work in this thesis provides tools and knowledge to advance the field of RNA and their proteins partners.

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