Roderick Hori, Ph.D.
858 Madison Ave.
301 Molecular Science Building
Memphis, TN 38163
Transcription is the first step in gene expression and the initiation of transcription is the most commonly regulated step in gene expression. Our goals are to understand the assembly, function and regulation of transcription initiation complexes, and to characterize transcriptional regulation in the antiviral response of interferon. We are working on four projects described below.
Project 1: Antiviral response of interferon
The antiviral activity of interferons depends on their ability to activate transcription of genes. Many viruses have developed strategies to inhibit or circumvent the interferon response. For example, the Matrix or M protein of vesicular stomatitis virus (VSV) represses host transcription by inactivating the TATA-Box Binding Protein (TBP). Despite the potential of M protein to inhibit the interferon system, the interferon response is critical for host defense against VSV. We are testing the hypothesize that interferon circumvents the activity of M protein using an unusual, but recently reported, mechanism of transcriptional activation that does not require TBP.
Project 2: Molecular mechanism of transcriptional activators
The goal of this project is to understand how activators stimulate transcription. Activators employ a variety of mechanisms. As one example, they stabilize assembly of the preinitiation complex (PIC) by directly interacting with components of the PIC. For protein-encoding genes, the PIC is composed of RNA polymerase (pol) II, Mediator complex, and general transcription factors such as TFIIA, TFIIB and TFIID. We are studying the molecular mechanisms that underlie the ability of transcriptional activation domains to function synergistically (i.e., a greater than additive response with respect to some property of activators or promoters), recruit the PIC and attempting to classify activation domains based on their mechanism of action.
Project 3: Mutually exclusive assembly of TBP-containing proteins
The goal of this project is to distinguish between two hypotheses that explain the mutually exclusive assembly of Selectivity Factor 1 (SL1) and TFIID (the TBP-containing proteins involved in RNA polymerase I and II transcription, respectively). TBP is required for expression by all three nuclear RNA polymerases and can be the limiting component. TBP is a subunit within at least five different protein complexes. If TBP were bound by subunits from different proteins, this would sequester TBP in non-productive complexes. It has been demonstrated that the subunits of SL1 and TFIID bind TBP in a mutually exclusive fashion. This is one mechanism that could prevent the formation of non-productive complexes. We are testing two hypotheses that could explain this phenomenon - 1) competition for overlapping binding sites and 2) conformational change.
Project 4: Localization of Selectivity Factor 1
The goal of this project is to determine the signals and proteins involved in targeting Selectivity Factor 1 to the nucleolus, the site of RNA polymerase I transcription. The SL1 TAFs are being examined for the presence of instrinsic nuclear and nucleolar targeting sequences, and the pathways that direct their subcellular localization.
- Ph.D., Biology, University of California, San Diego, 1992
- B.S., Biochemistry, University of California, Los Angeles, 1985