Biochemistry Seminar Dr. Michelle Scott
Dr. Michelle Scott
PhD
College of Life Sciences
University of Dundee, United Kingdom
鈥淏ioinformatic characterization of the nucleolus鈥�
听
Although primarily known for its role in the biogenesis of ribosomes, the nucleolus is involved in numerous other fundamental cellular activities, including cell cycle progression, proliferation regulation and the response to numerous forms of cellular stress. Recent large scale proteomics projects have identified thousands of nucleolar-associated proteins, many of which are dynamically localized to this compartment under different conditions, revealing cyclical and conditional nucleolar association. To understand the numerous roles of the nucleolus in the cell, it is necessary to define the complete dynamic nucleolar proteome and characterize its resulting interaction network.
听
To address these questions, we have investigated the most well-known form of targeting to the nucleolus and created an artificial neural network predictor of nucleolar localization sequences (NoLSs). We predict over 50% of proteins annotated as nucleolar in Uniprot to harbour a NoLS, suggesting this is a widely used mechanism. We have also investigated the extent of nucleolar association of human proteins by integrating gene and protein characteristics into a probabilistic framework, thus extending the coverage of the nucleolar proteome past the current experimental detection limits. These predictions reveal that approximately 15% of human proteins are nucleolar-associated and that this group is significantly more evolutionarily conserved than non-nucleolar proteins. This characterization of the complete dynamic nucleolar proteome has been used to filter and annotate our human predicted interactome (), which will be augmented to include the known nucleolar RNA content and its relationship to the nucleolar proteome.
听
听
Scott MS, Avolio F, Ono M, Lamond AI, Barton GJ (2009), Human miRNA precursors with box H/ACA snoRNA features, PLoS Comp Biol, 5(9):e1000507.
听
McDowall MD, Scott MS, Barton GJ, (2009) PIPs: human protein-protein interaction prediction database, Nucleic Acids Research, 37(Database issue):D651-6.
听
Scott MS and Barton GJ (2007) Probabilistic prediction and ranking of human protein-protein interactions, BMC Bioinformatics 8(1):239.
听
Scott M, Boisvert FM, Vieyra D, Johnston RN, Bazett-Jones DP, Riabowol K, (2001), UV induces nucleolar translocation of ING1 through two distinct nucleolar targeting sequences, Nucleic Acids Research, 29(10): 2052-8.