Selected Recent PublicationsFeb 2014Makrantoni, V., Corbishley, S. J.,Rachidi, N.,Morrice, N. A., Robinson, D. A. and Stark, M. J. R. Phosphorylation of Sli15 by Ipl1 is important for proper CPC localization and chromosome stability in Saccharomyces cerevisiaePLoS One. 2014;9(2):e89399. doi: 10.1371/journal.pone.0089399 PMID: 24558497 AbstractView PublicationMay 2014Di Santo, R., Bandau, S. and Stark, M. J. R. A conserved and essential basic region mediates tRNA binding to the Elp1 subunit of the Saccharomyces cerevisiaeElongator complexMol Microbiol. 2014;92(6):1227-42. doi: 10.1111/mmi.12624 PMID: 24750273 AbstractView PublicationNov 2015Abdel-Fattah, W., Jablonowski, D., Di Santo, R., Thuring, K. L., Scheidt, V., Hammermeister, A., Ten Have, S., Helm, M., Schaffrath, R. and Stark, M. J. Phosphorylation of Elp1 by Hrr25 is required for Elongator-dependent tRNA modification in yeast PMID: 25569479 AbstractView PublicationFeb 2013Uthman, S., Bär, C., Scheidt, V., Liu, S., ten Have, S., Giorgini, F., Stark, M. J. R. and RaffaelSchaffrath, R. The amidation step of diphthamidebiosynthesis in yeast requires DPH6, a gene identified through mining the DPH1-DPH5interaction networkPLoS Genetics. doi. 10.1371/journal.pgen.1003334 PMID: 23468660 AbstractView PublicationJun 2009Makrantoni, V. and Stark, M. J. R. Efficient chromosome bi-orientation and the tension checkpoint in Saccharomyces cerevisiae both require Bir1Molecular and Cellular Biology. 29, (16) 4552-4562 PMID: 19528231 AbstractView Publication Elongator-dependent tRNA wobble uridine modification Most processes required for the function and the survival of cells are carried out by proteins, polymers made up of building blocks termed amino acids. Small RNA molecules (tRNAs) are used to shuttle amino acids to the cellular machinery that synthesises proteins. Our interest is in a mechanism that affects the efficiency with which some of the tRNAs function. We would like to understand whether cells can use this mechanism to change the spectrum of proteins that they make. Over the past 29 years my laboratory has used the yeast Saccharomyces cerevisiae as a model organism for investigating processes that are important for cell growth and division. My current focus is on Elongator, a protein complex containing six different polypeptides that is responsible for chemical modification of uridine residues present at the ‘wobble’ position of the anticodon (U34) in a subset of tRNAs. These Elongator-dependent modifications to U34 (termed mcm5U and ncm5U) are required for wobble uridine-containing tRNAs to function efficiently in protein synthesis. Elongator is essential for mammalian development and defects in Elongator are associated with Familial Dysautonomia, a neurodevelopmental disease. The Elp1 component of yeast Elongator is phosphorylated by the casein kinase I orthologue Hrr25 and we have recently shown that Elongator-dependent U34 modification requires this phosphorylation. We are currently interested in understanding in molecular terms how Elp1 phosphorylation promotes Elongator function, and in particular whether Elp1 phosphorylation represents a mechanism that functions to regulate protein synthesis through modulating the functionality of U34-containing tRNAs. Elp1 contains a tRNA binding domain adjacent to the phosphorylated region and we would also like to understand whether there is a functional relationship between Elp1 phosphorylation and tRNA binding. Recent work in Archaea demonstrated that the archaeal orthologue of Elp3 is responsible for U34 modification. Since Archaea lack orthologues of the other five Elongator subunits that are essential for U34 modification in Eukaryotes, we are interested in understanding why U34 modification in higher organisms requires such complexity.