Professor In Molecular Genetics & Microbiology, Under Graduate Advisor
Main Office: NMS 1.126
Phone: (512) 475-6350
Alternate Office: NMS 1.246
Alt. Phone: (512) 475-9729
The University of Texas at Austin
Section of Molecular Genetics and Microbiology
2506 Speedway Stop A5000
Austin ,TX 78712-1191
Research SummarySince working out the pathway for nuclear export of the large ribosomal subunit more than 10 years ago, we have continued to study both nuclear and cytoplasmic events of making ribosomes (Lo et al Mol Cell, 2010). We have become interested in the general question of how the newly made ribosome is checked for function. We have found that the proper assembly of the P-site, close to the catalytic center of the ribosome is assessed by several proteins that appear to be mimics of translation factors (Bussiere et al J Cell Bio, 2012). This has led us to propose that the 60S subunit undergoes a "test drive' that involves a pseudo translocation event before it is released into the pool of active ribosomes. We are continuing to pursue this interface between ribosome biogenesis and translation.
Ribosomal mutations that disrupt this test drive are associated with Acute T-cell leukemia (De Keersmaecker et al Nat Gen 2013). We are using yeast as a model for these T-ALL mutations to understand the impact of failing in this quality control step. In particular, we are interested in translational fidelity defects caused by these mutations.
In contrast to the large subunit of the ribosome, which catalyzes polypeptide synthesis, the small subunit is responsible for decoding. A new project in my lab is directed at understanding the events that promote the critical event of separating the small subunit from the large subunit in the nucleus. We have proposed that this event is controlled by proteins that assess the status of assembly of the subunit, ensuring that cleavage occurs only after completing the major assembly events of the small subunit.