Susan J Baserga, MD, PhD

Professor of Molecular Biophysics and Biochemistry, of Genetics and of Therapeutic Radiology

Research Interests

Biogenesis; Genetics; Molecular Biology; Ribonucleoproteins; Radiation Oncology; RNA Helicases; Genes, rRNA; Biochemical Processes

Research Organizations

Molecular Biophysics and Biochemistry: Baserga Lab | RNA Biology

Therapeutic Radiology: Radiobiology

Cancer Center: Genomics, Genetics, and Epigenetics

Center for RNA Science and Medicine, Yale

Faculty Research

Gene Regulation and Functional Genomics

Liver Center

Radiobiology and Radiotherapy

Office of Cooperative Research

Research Summary

Of Yeast and Ribosome Biogenesis: Ribosome biogenesis is a complex process requiring the coordinated expression of rRNA and protein moieties and their assembly in the eukaryotic nucleolus. In order to better understand each aspect of this process, we are using an array of genetic, biochemical, and cell biological techniques in the yeast Saccharomyces cerevisiae. My laboratory focuses on the role of the ribonucleoprotein and protein complexes involved in generating the mature rRNAs.

Specialized Terms: Ribosome biogenesis; RRNA processing; U3 RNP structure and function; RNA helicases; Polymerase I transcription and processing

Extensive Research Description

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.

Using innovative proteomics techniques, my laboratory has recently identified the protein components of a large nucleolar ribonucleoprotein that is required for processing of the 18S small subunit 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 18S 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.

Through these studies we have discovered and characterized several unique protein motifs and their specific roles in rRNA processing. We have recently discovered that a subset of the SSU processome proteins are associated with the rDNA and are required for rDNA transcription. Stemming from this idea, we are interested in studying the proteins which regulate transcription of the rDNA by Pol I and initiate the processing of the rRNA. We have learned that these steps are intimately linked, and endeavor to describe this complex process in detail. Seventeen putative RNA helicases have been shown to be required for processing of the small and large ribosomal subunit RNAs, perhaps by remodeling the rRNA to allow access to cleavage sites. Ongoing genetic and biochemical studies in the lab examine the roles of each putative RNA helicase and test its ability to unwind RNA. Through these projects, we strive to ascertain how and why the helicases are required at each step in ribosome biogenesis. Because ribosomes are essential to cell growth via the production of new proteins, we are studying the role of ribosome biogenesis in cell cycle regulation.

We have previously shown that rRNA maturation by the SSU processome is required for cell cycle progression, indicating that the production of ribosomes has a distinct influence on the cell cycle. Specifically, we seek to find the ribosome-regulated trigger that allows the cell to progress through the cell cycle, grow in size, and divide. Transcription of the rDNA and processing of the rRNA can be visualized in Miller chromatin spreads, as shown here. In a, the SSU processome corresponds to the terminal knobs at the end of each rRNA branching off the rDNA. When components of the SSU processome are depleted (the U3 snoRNA in b, or the Utp7 protein in c), the knobs are no longer present, due to incomplete formation of the SSU processome.

Selected Publications

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