William Stumph

Email

Primary Email: [email protected]

Phone/Fax

Primary Phone: 42422

Building/Location

5500 Campanile Dr
San Diego, CA 92182
Mail Code: Links

Bio

Research in Dr. Stumph's lab is aimed at understanding the molecular mechanisms of gene expression in higher organisms. Dr. Stumph's group has been characterizing and studying the expression of genes that code for the small nuclear RNAs (snRNAs) known as U1, U2, U4, U5, and U6. These genes code for RNA molecules with such fundamental importance to cellular metabolism, and their expression appears to be controlled by unique mechanisms. To understand how the same protein can in one case recruit RNA polymerase II (for U1 transcription) but in another case recruit RNA polymerase III (for U6 transcription), we apply various biochemical and molecular biological techniques to the study of the Drosophila system. We have shown that the 5 nucleotide differences between the U1 and U6 PSEAs are sufficient to determine the RNA polymerase specificity of the U1 and U6 gene promoters. Furthermore, by site-specific protein-DNA photocrosslinking techniques, we have determined that DmSNAPc consists of at least three distinct polypeptide chains that contact the DNA of the PSEA. Significantly, the data also reveal that the precise contacts made between the protein and the DNA are different depending upon whether DmSNAPc is bound to a U1 or U6 PSEA sequence. From these data, we have proposed that the U1 and U6 PSEA sequences act as differential allosteric effectors of DmSNAPc. According to this model, when DmSNAPc binds to a U1 PSEA sequence, it adopts a conformation that allows it to recruit only RNA polymerase II basal factors during subsequent steps of pre-initiation complex assembly. On the other hand, when DmSNAPc binds to a U6 PSEA, it adopts a conformation compatible with the recruitment of only RNA polymerase III basal factors. We are currently making mutations in these various subunits to identify domains within the proteins that are required for complex assembly, DNA binding, and the activation of transcription. One goal is to identify mutations that will result in the loss of activation of transcription by one RNA polymerase but not the other. In this way, we hope to identify domains within the proteins that are specifically required for transcription by one RNA polymerase but not the other.

Areas of Specialization

Biochemistry, Synthetic Organic Chemistry