Pilot Project E: The Role of Phosphorylation in the NMD RNA Surveillance Mechanism
Co-Investigators
Carlos Gonzalez, Ph.D., Assistant Professor, Department of Biology, University of Puerto Rico-Rio Piedras, Rio Piedras, Puerto Rico
Miles Wilkinson, Ph.D., Professor, Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, Texas
This proposal concerns an RNA surveillance pathway known as nonsense-mediated mRNA decay (NMD) that degrades transcripts harboring premature termination codons (PTCs). One third of inherited human genetic diseases are caused by frameshift or nonsense mutations that generate PTCs. Nonsense codons also arise frequently during the normal programmed rearrangement events that occur in the immunoglobin (lg) and T-cell receptor (TCR) genes (frameshift-generating rearrangements occur two thirds of the time).
Specific Aims
- Map the phosphorylation site(s) of yeast Upf1p
- Elucidate the functional role of Upf1p phosphorylation in NMD