David A. Brow

Credentials: RNA biology and gene expression in eukaryotes

Position title: Professor

Email: dabrow@wisc.edu

Phone: (608) 262-1475

Address:
4204B Biochemical Sciences Building
440 Henry Mall, Madison, WI 53706

The Brow Lab Website

Education

BA 1979, University of California, Santa Cruz (Harry Noller)
PhD 1986, University of California, San Diego (E. Peter Geiduschek)
Postdoctoral, 1986-89, University of California, San Francisco (Christine Guthrie)

Honors & Awards

1990 Searle Scholars Award (Chicago Community Trust)
1991 Shaw Scientist Award (Milwaukee Foundation)
1999 Vilas Associate Award, University of Wisconsin-Madison
2001 University of Wisconsin Medical School Dean’s Teaching Award
2016 Elected fellow, American Academy of Microbiology
2016 Chancellor’s Distinguished Teaching Award, University of Wisconsin-Madison
2016 Elected fellow, American Association for the Advancement of Science

Research Interests

We study two essential biological “nanomachines” of gene expression, the spliceosome and RNA polymerase II (Pol II), using brewer’s yeast as a model system. Our studies on the spliceosome focus on U6 RNA and the dynamic RNA-RNA and RNA-protein interactions required for its assembly into the active site. Using genetic suppression analysis and in vitro biochemistry, we have defined a complex network of interactions that involves 3 RNAs (U2, U4, and U6), two helicases (Prp28 and Brr2), an RNA-binding protein (Prp24), and the largest and most conserved spliceosomal protein (Prp8). In collaboration with Sam Butcher’s lab, we recently solved the crystal structure of the core U6 snRNP (Prp24 bound to U6 RNA) at 1.7 Å resolution (see Figure 1).figure-1Figure 1. From EJ Montemayor et al. (2014) Nature Struct. Molec. Biol. 21: 544-551.Our work on Pol II focuses on transcription termination as a strategy for gene regulation. We discovered and are characterizing a pathway that uses the helicase Sen1 and a collection of RNA-binding proteins, including Nrd1 and Nab3, to terminate synthesis of short transcripts by Pol II (see Figure 2). This pathway aids in the synthesis of non-coding RNAs, as well as the regulation of mRNA levels. Mutations in the human homolog of Sen1 result in neuro-degenerative disorders. We are exploring the function and targets of the Sen1 termination pathway by genetics, genomics, biochemistry, and structural biology.
brow-2Figure 2. From DA Brow (2011) Molec. Cell 42: 717-718.

Publications

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