David Morris
	Professor of Biochemistry       206.543.1694 V       206.543.4822 F       dmorris@u.washington.edu

Research

Regulation of mRNA translation into protein provides a mechanism for a cell to rapidly and massively alter its proteome in response to changes in the physical, chemical and biological environment. Translational control plays an important role throughout nature, from unicellular organisms to Metazoans. Our group is interested in those features of mRNA structure - cis elements - that confer unique regulatory properties upon transcripts (Morris, 1997). Examples of these elements are binding sites for translational repressor proteins (Kaspar et al., 1992) and small open reading frames located within the 5 leaders of mRNAs (Raney et al., 2002;Jin et al., 2003).

A second interest of our group is how the translation of individual mRNAs is coordinated at a transcriptome-wide level, to form regulatory networks. The exploration of this second area has necessitated the development of tools for evaluating translational control at the genome scale (http://faculty.washington.edu/dmorris/index2.html). Through these studies, using Saccharomyces cerevisiae as a model organism, we have found groups of functionally related mRNAs that are poorly translated in non-stressed cells, but are poised to recruit ribosomes in response to the appropriate external stimulus (Serikawa et al., 2003;MacKay et al., 2004).

Examples of these classes of poised transcripts are those that encode proteins involved in cellular responses to mating pheromone, nitrogen starvation and osmotic stress. We are currently studying the mechanisms through which these coordinated regulatory responses are mediated.

Selected Publications

Jin, X., E.Turcott, S.Englehardt, G.J.Mize, and D.R.Morris. 2003. The two upstream open reading frames of oncogene mdm2 have different translational regulatory properties. J. Biol. Chem. 278:25716-25721.

Kaspar, R.L., T.Kakegawa, H.Cranston, D.R.Morris, and M.W.White. 1992. A regulatory cis element and a specific binding factor involved in the mitogenic control of murine ribosomal protein L32 translation. J. Biol. Chem. 267:508-514.

MacKay, V.L., X.Li, M.R.Flory, E.Turcott, G.L.Law, K.A.Serikawa, X.L.Xu, H.Lee, D.R.Goodlett, R.Aebersold, L.P.Zhao, and D.R.Morris. 2004. Gene expression in yeast responding to mating pheromone: Analysis by high-resolution translation state analysis and quantitative proteomics. Mol. Cell. Proteomics 3:478-489.

Morris, D.R. 1997. Cis-acting mRNA structures in gene-specific translation control. In RNA metabolism and post-transcriptional gene regulation. J.B.Harford and D.R.Morris, editors. Wiley-Liss, Inc., New York. 165-180.

Raney, A., G.L.Law, G.J.Mize, and D.R.Morris. 2002. Regulated translation termination at the upstream open reading frame in S-adenosylmethionine decarboxylase mRNA. J. Biol. Chem. 277:5988-5994.

Serikawa, K.A., X.L.Xu, V.L.MacKay, G.L.Law, Q.Zong, L.P.Zhao, R.Bumgarrner, and D.R.Morris. 2003. The transcriptome and its translation during recovery from cell-cycle arrest in Saccharomyces cerevisiae. Mol. Cell. Proteomics 2:191-204.