Post-Translational Protein Modification by SUMO

Post-translational modification of proteins by the small ubiquitin-like modifier SUMO regulates many cellular processes, including nuclear transport, stress response, and signal transduction in eukaryotes. SUMO modification also appears to be essential for cell cycle progression in yeast and higher eukaryotes. Like ubiquitin modification, covalent attachment of SUMO to protein targets occurs on lysine residues. SUMO modification is reversible, altering target protein function through changes in cellular localization, biochemical activation, or through protecting the substrate from other post-translational protein modifications.

RNA Decay

Cellular RNA levels are regulated by maintaining balance between transcription and degradation pathways. While several key enzymes and regulators have been identified in RNA degradation pathways, their precise activities in the pathway remain less clear. One of these is the RNA exosome, a multi-subunit protein complex that is involved in several 3’ to 5’ RNA decay pathways. The exosome is conserved throughout eukaryotic evolution and is thought to exist in at least two forms, a cytoplasmic exosome composed of nine or ten individually encoded subunits, and a nuclear exosome composed of the cytoplasmic exosome plus an additional nuclear subunit. The exosome is essential in budding yeast insomuch as ten of the eleven subunits are essential for growth, suggesting that most subunits perform critical functions in vivo for exosome assembly or for RNA decay activities.

RNA Processing and Repair

Eukaryotic messenger RNA requires the addition of a nucleotide cap for proper function in the cell. We are interested in understanding the molecular basis for cap maturation and how those enzymes are regulated in the cell, especially through their recruitment to the transcription apparatus. In addition to studies addressing cap formation, we have also focused our attention to those enzymes involved in cap degradation. Our interest in RNA processing also extends to RNA repair. In collaboration with the Shuman laboratory, we have addressed the structural basis for RNA repair through the structure determination of RNA ligase intermediates.

Other Interests

In collaboration with the Nathan Lab at the Weill Medical College of Cornell University, the laboratory is working on several enzymes that are responsible for antioxidant defense in Mycobacterium tuberculosis.