|Elongator is a six-subunit protein complex first discovered in yeast but conserved throughout eukaryotes. Although initially proposed to promote efficient transcription, Elongator is now known to be required for addition of 5-methoxycarbonymethyl and 5-carbamoylmethyl modifications to uridine residues in the anticodon wobble position of tRNAs that decode synonymous codons ending in purines (1, 2). These Elongator-dependent wobble uridine modifications enable them to function properly in translation, accounting for the diverse range of phenotypes that are associated with loss of Elongator function. Although nonessential in yeast, deletion of the gene for its largest subunit (Elp1) in mouse is embryonic lethal while mutations in the human Elp1 homologue are responsible for Familial Dysautonomia, a severe recessive neurodevelopmental condition (3). The Elp1 subunit of Elongator is phosphorylated and by studying yeast Elongator in collaboration with the laboratory of Raffael Schaffrath (University of Kassel) we have identified protein kinases and phosphatases that regulate Elongator (4) and sites of phosphorylation on Elp1 that are functionally important. We have recently identified a domain in Elp1 that interacts with tRNA (5) and our current research seeks to understand the role of Elp1 phosphorylation in Elongator function and its relationship to the binding of tRNA by Elp1.
- Huang, B., Johansson, M. J. and Bystrom, A. S. (2005). An early step in wobble uridine tRNA modification requires the Elongator complex. RNA 11, 424-436.
- Glatt, S., Seraphin, B. and Muller, C. W. (2012). Elongator: transcriptional or translational regulator? Transcription 3, 273-276.
- Slaugenhaupt, S.A. and Gusella, J.F. (2002). Familial dysautonomia. Curr. Opin. Genet. Devel. 12, 307-311.
- Mehlgarten, C., Jablonowski, D., Breunig, K. D., Stark, M. J. R. and Schaffrath, R. Elongator function depends on antagonistic regulation by casein kinase Hrr25 and protein phosphatase Sit4. (2009). Mol Microbiol 73, 869-881.
- Di Santo, R., Bandau, S. and Stark, M. J. R. (2014). A conserved and essential basic region mediates tRNA binding to the Elp1 subunit of the Saccharomyces cerevisiae Elongator complex. Mol. Microbiol. 92, 1227-1242.
- Abdel-Fattah, W. R., Jablonowski, D., Di Santo, R. T. A., Thüring, K. L., Scheidt, V., ten Have, S. M., Helm, M., Schaffrath, R. and Stark, M. J. R. (2015). Phosphorylation of Elp1 by Hrr25 is required for Elongator-dependent tRNA modification in yeast. PLoS Genet 11 (1), e1004931.