Stephen M. Mount

Associate Professor

Ph.D., Yale, 1983
Phone: (301) 405-6934
URL:www.SteveMount.org
E-mail:smount@umd.edu

Research Interests: Molecular Genetics. Pre-mRNA splicing.


Research in the Mount lab is devoted to understanding how multicellular organisms accomplish the correct processing of RNA from protein-coding genes. This involves identifying the elements of primary sequence information that determine where (and whether or not) splicing will occur, determining which components of the splicing machinery play especially salient roles in recognizing those signals, and determining how those factors act.


Our Arabidopsis research is focused on the identification of sequences within exons that may act to enhance splicing (such sequences are known as exonic splicing enhancers, or ESEs). ESEs are best characterized in animal systems, and research on plant pre-mRNA splicing has emphasized the role of AU-rich or U-rich sequences within introns, there are compelling reasons to believe that ESEs also play an important role in plant splicing. In particular, SR proteins, the mediators of ESE activity in animals, are highly conserved. This research is funded by a grant from the NSF under the 2010 program in collaboration with co-PIs Caren Chang at Maryland and Steven Salzberg at TIGR.

Image courtesy of Cartegni et al.:

The bulk of our research has been in the molecular genetics of splicing factors in the fruit fly Drosophila melanogaster. We are currently focused on B52 and U1 70K, two factors that function in splice site selection. Earlier screens for mutations in genes that play key roles in RNA processing decisions led to the isolation of B52ED, a dominant mutation in B52, the gene for an essential SR protein splicing factor. This dominant mutation is a single amino acid change in the RNA-binding domain that results in altered RNA-binding specificity. Null alleles in B52, are lethal. However, the lethal phase is surprisingly late (second instar larvae), and clones of cells that are homozygous for null alleles of B52 are viable. U1 70K is a protein component of the U1 small nuclear ribonucleoprotein. Like B52, U1 70K is highly conserved, and is known to participate in the early stages of splicing, when splice selection is accomplished. Interactions between U1 70K and SR proteins mediated by arginine-rich domains in both proteins have been described in the literature. To our surprise, null alleles of 70K can be complemented by trangenes lacking this domain, a result suggests that this interaction cannot be essential for overall splicing fidelity.

We have conducted a phylogenetic analysis of SR protein genes in complete eukaryotic genomes (Saccharomyces, Schizosaccharomyces, Caenorhabditis, Drosophila, Arabidopsis and Homo). This analysis reveals that SR proteins are diverse, and that specific SR protein subfamilies have been present since the last common ancestor of animals, plants and fungi. It is striking that the plant Arabidopsis has more SR protein genes than any other known organism by a factor of two (20 genes in Arabidopsis vs. 9 in humans).

Representative Publications:

Salz et al. 2004. The Drosophila U1-70K protein is required for viability, but its arginine-rich domain is dispensable. Genetics.168:2059-65.

Nagengast et al. 2003. Sex-lethal splicing autoregulation in vivo: interactions between SEX-LETHAL, the U1 snRNP and U2AF underlie male exon skipping.Development 140: 463-471.

Adams et al. 2000. The genome sequence of Drosophila melanogaster. Science 287:2185-2195.

Mount, S.M. and H.K. Salz. 2000. Pre-messenger RNA processing factors in the Drosophila genome. J. Cell Biol. 150:F37-F43.

Mount 2000. Genomic sequence, splicing, and gene annotation. Amer. J. Human. Genet. 67:788-792.

Peng, X. and S. M. Mount. 1995. Genetic enhancement of RNA-processing defects by a dominant mutation in B52, the Drosophila gene for an SR protein splicing factor. Mol. Cell. Biol. 15: 6273-6282.

Lo, P., D. Roy, and S. M. Mount. 1994. Suppressor U1 snRNAs in Drosophila melanogaster. Genetics 138: 365-378.

Guo, M., P. C. H. Lo and S.M. Mount. 1993. Species-specific signals for the splicing of a short Drosophila intron in vitro. Mol. Cell. Biol. 13: 1104-1118.

Mount, S.M., C. Burks, G. Stormo, J. Hertz and C. Fields. 1992. Splicing signals in Drosophila: intron size, information content, and consensus sequences. Nucleic Acids Res. 20: 4255-4262.

Current undergraduate students:

  • Aileen Pan
  • Sita Marie Shablack
  • Sangeetha Raghavan
  • Nicolas Tilmans
  • Yun Choi

    Current graduate students:

    Jason Edmonds (Cell Biology and Molecular Genetics)

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