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SUSAN BASERGA

Ribosome biogenesis is a complex process requiring the coordinated expression of rRNA and protein moieties and their assembly in the eukaryotic nucleolus. Using innovative proteomics techniques, my laboratory has recently identified the protein components of a large nucleolar ribonucleoprotein that is required for processing of precursors to the 18S small subunit's rRNA. This RNP, which we termed the SSU processome, is composed of the U3 snoRNA and 40 proteins. Currently, projects in the lab are aimed at determining the architecture of this RNP and the functions of individual proteins in pre-18S rRNA processing. We approach this question from several perspectives, using genetic and biochemical methods to identify direct interactions between components and cryo-electron microscopy to visualize the complex in three dimensions. Previous and ongoing projects in the lab include:

• study of RNA helicases required for ribosome biogenesis and their cofactors
  
• investigations into the role of ribosome biogenesis in cell cycle regulation
  
• discovery of a subset of SSU processome proteins that are associated with the rDNA and are required for rDNA transcription
  
• identifying subcomplexes of the SSU processome and deciphering the direct protein-protein and protein-RNA interactions that mediate their assembly
  
• purification and electron microscopy to visualize pre-ribosomes
  
• characterization of an essential new protein-protein interaction motif found in RNA processing RNPs
  
• developing a method to identify individual proteins in chromatin spreads

Selected publications
Dragon, F., Gallagher, J. E., Compagnone-Post, P. A., Mitchell, B. M., Porwancher, K. A., Wehner, K. A., Wormsley, S., Settlage, R. E., Shabanowitz, J., Osheim, Y., Beyer, A. L., Hunt, D. F. and Baserga, S. J. A large nucleolar U3 ribonucleoprotein required for 18S ribosomal RNA biogenesis. Nature 417, 967-970 (2002)

Gallagher, J. E., Dunbar, D. A., Granneman, S., Mitchell, B. M., Osheim, Y., Beyer, A. L. and Baserga, S. J. RNA polymerase I transcription and pre-rRNA processing are linked by specific SSU processome components. Genes Dev. 18, 2506-2517 (2004)

Bernstein, K. A., Granneman, S., Lee, A. V., Manickam, S. and Baserga S. J. Comprehensive mutational analysis of yeast DExD/H box RNA helicases involved in large ribosomal subunit biogenesis. Mol. Cell. Biol. 4, 1195-1208 (2006)

Bleichert, F., Granneman, S., Osheim, Y. N., Beyer, A. L. and Baserga, S. J. The PINc domain protein Utp24, a putative nuclease, is required for the early cleavage steps in 18S rRNA maturation. Proc. Natl. Acad. Sci. U S A. 103, 9464-9469 (2006)

Granneman, S., Lin, C., Champion, E. A. Nandineni, M. R. Zorca, C. and Baserga, S. J. The nucleolar protein Esf2 interacts directly with the DExD/H box RNA helicase, Dbp8, to stimulate ATP hydrolysis. Nucleic Acids Res. 34, 3189-3199 (2006)

Last Updated 12-18-06