Ph.D. (1984) University of Illinois, Urbana	Scott Butler   Associate Professor of Microbiology & Immunology, and of Biochemistry & Biophysics Primary Appointment:   Microbiology & Immunology Graduate Programs   BMCB - Biochemistry, Molecular and Cellular Biology   IMV - Immunology, Microbiology, and Virology
	Contact Information:
	University of Rochester School of Medicine and Dentistry 601 Elmwood Ave, Box 672 Rochester, New York 14642	Phone: (585) 275-7921 Fax: (585) 473-9573 E-Mail: Scott_Butler@urmc.rochester.edu

Research Focus

Post-transcriptional Regulation of mRNA Expression in the Nucleus of Eukaryotic Cells.

Research Overview

The biogenesis of mature eukaryotic RNAs requires post-transcriptional processing reactions that provide targets for the regulation of gene expression. Little is known about how RNA processing pathways are co-regulated to produce balanced levels of mature RNAs in response to changes in the cell¹s intracellular and extra-cellular environment. The research in my laboratory focuses on the roles of nuclear proteins implicated in the post-transcriptional regulation of mRNA and rRNA levels in S. cerevisiae. Recent experiments from our laboratory and others has identified a large complex of riboexonucleases, called the exosome, that exists in the nucleus and the cytoplasm and is required for the processing of all types of RNA molecules, except tRNAs. The riboexonuclease Rrp6p, a component of the nuclear exosome, is a hydrolytic enzyme that degrades RNA molecules in a 3¹-5¹ direction. Our studies show that Rrp6p plays a role in rRNA processing, ribosome biogenesis, and in nuclear mRNA degradation pathway that destroys slowly, or improperly processed mRNAs. Current research in our laboratory seeks an understanding of the biochemical mechanism and physiological function of Rrp6p. These studies include; (i) affinity purification and genetic experiments to determine the structural and functional relationship between Rrp6p and other proteins, including hnRNP proteins and core components the exosome, (ii) biochemical analysis of the exonuclease activity of Rrp6p and analysis of domains required for interaction with other proteins and (iii) identification and analysis of natural substrates of the nuclear mRNA decay pathway by genome-wide microarray analysis.

Recent Publications

Callahan KP, Butler JS. Lifting the veil on the transcriptome. Genome Biol. 2008 Apr 24;9(4):218

Fang F, Phillips S, Butler JS.  "Rat1p and Rai1p function with the nuclear exosome in the processing and degradation of rRNA precursors." RNA. 2005 Oct;11(10):1571-8. Epub 2005 Aug 30.

Roth, K. M., M. K. Wolf, et al. "The nuclear exosome contributes to autogenous control of NAB2 mRNA levels." Mol Cell Biol 25(5): 1577-85, 2005.

Fang, F., J. Hoskins, et al. "5-fluorouracil enhances exosome-dependent accumulation of polyadenylated rRNAs." Mol Cell Biol 24(24): 10766-76, 2004.

Lum PY, Armour CD, Stepaniants SB, et al. "Discovering modes of action for therapeutic compounds using a genome-wide screen of yeast heterozygotes." Cell. 116:121-37, 2004.

Das B, Butler JS, Sherman F. "Degradation of Normal mRNA in the Nucleus of Saccharomyces cerevisiae" Mol. Cell. Biol. 23 5502-5515, 2003.

Burkard KT, Butler JS. A nuclear 3'-5' exonuclease involved in mRNA degradation interacts with Poly(A) polymerase and the hnRNA protein Npl3p. Mol Cell Biol. 20:604-16, 2000.

Briggs MW, Burkard KT, Butler JS. Rrp6p, the yeast homologue of the human PM-Scl 100-kDa autoantigen, is essential for efficient 5.8 S rRNA 3' end formation. J Biol Chem. 273:13255-63, 1998.

Liang S, Briggs MW, Butler JS. Regulation of tRNA suppressor activity by an intron-encoded polyadenylation signal. RNA. 1997 Jun;3(6):648-59.

Proweller A, Butler JS. Ribosome concentration contributes to discrimination against poly(A)- mRNA during translation initiation in Saccharomyces cerevisiae. J Biol Chem. 272:6004-10, 1997.

Briggs MW, Butler JS. RNA polymerase III defects suppress a conditional-lethal poly(A) polymerase mutation in Saccharomyces cerevisiae. Genetics. 143:1149-61, 1996.

Proweller A, Butler JS. Ribosomal association of poly(A)-binding protein in poly(A)-deficient Saccharomyces cerevisiae. J Biol Chem. 271:10859-65, 1996.

Review Articles

Butler JS. The yin and yang of the exosome. Trends Cell Biol. 12:90-6, 2002.

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