Professor Mike Stark

FRSB

Emeritus Professor of Yeast Molecular Biology

Gene Regulation and Expression, School of Life Sciences

portrait of Mike Stark
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Contact

Email

m.j.r.stark@dundee.ac.uk

Phone

+44(0)1382 385828

Research

The availability of powerful classical and molecular genetic methodologies, a well annotated genome and the ability to carry out sophisticated biochemistry and cell biology make the yeast Saccharomyces cerevisiae a valuable model organism in which to study conserved regulatory mechanisms. A surprisingly large number of fundamental cellular processes are conserved between yeast and higher eukaryotes and I am interested in studying those molecular mechanisms that regulate growth and division using Saccharomyces cerevisiae as a model system.

My recent research has focused on Elongator, a conserved, six-subunit protein complex. Although Saccharomyces cerevisiae Elongator is non-essential for growth in the laboratory, it is essential for mammalian development and mutations in its Elp1 subunit are associated with Familial Dysautonomia, a neurodevelopmental disease. Over the past decade a variety of roles have been proposed for Elongator, but the principal and possibly only role of Elongator is to promote two related chemical modifications to the uridine residue that is present at the anticodon ‘wobble’ position (U34) in a subset of tRNAs. These U34 modifications (termed mcm5U and ncm5U) are required for wobble uridine-containing tRNAs to function efficiently in protein synthesis, and Elongator’s role in wobble uridine modification is conserved in plants, worms (C. elegans) and mammals.

Yeast Elp1 shows Hrr25-dependent phosphorylation and we have shown recently that this is required for Elongator functionality. Hrr25, a yeast casein kinase I orthologue, directly phosphorylates Elp1 and Elongator-dependent tRNA wobble uridine modification depends on phosphorylation of the Hrr25 sites along with other, adjacent phosphorylation sites that are not directly phosphorylated by Hrr25. The phosphorylated region is adjacent to a domain in Elp1 that we have shown to bind tRNA and we would like to understand, in molecular terms, how these phosphoregulatory and tRNA binding domains in Elp1 cooperate to promote wobble uridine modification, which is likely to be catalyzed by Elongator’s Elp3 subunit.