Genetic and biochemical analysis of selenoprotein biosynthesis in Archaea (B 11)

• Subject Area: Biochemistry
• Term: from 2007 to 2009
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5484731

Proteins that contain selenocysteine, the 21st co-translationally inserted amino acid, arepresent in members of all three domains of life. The universal codon for selenocysteine is theopal (stop-) codon UGA on the mRNA. To mediate receding of the stop codon into a sensecodon, the presence of a secondary structure on the selenoprotein mRNA (the SECIS element)is required. While the mechanism of selenocysteine biosynthesis and its incorporation intonascent polypeptides is well understood in bacteria such as E. coli, surprisingly large gapsexist in the understanding of the archaeal and the eukaryal system. From what is known it isapparent that striking similarities exist in the process of selenoprotein biosynthesis of thelatter two domains. Thus, insights gained in one system are potentially applicable in the othersystem. Methanococcus maripaludis, a mesophilic, fast growing methanogenic archaeon is anexcellent model to study the mechanisms of selenoprotein biosynthesis in Archaea. It is theonly known selenoprotein-containing archaeon for which a facile system for genetic analysesis established. Furthermore, all of its selenoproteins were shown to be non-essential undercertain conditions. In the course of the proposed research the pathway of selenocysteinebiosynthesis and incorporation of M. maripaludis will be investigated by genetic andbiochemical approaches. Phenotypical analyses of mutants unable to synthesizeselenoproteins as well as biochemical analyses of gene products involved, will, beside theobvious value of the new insights, also lead to a better understanding of the less tractableeukaryal system.

• DFG Programme: Collaborative Research Centres
• Subproject of: SFB 579: RNA-Ligand Interactions
• Applicant Institution: Goethe-Universität Frankfurt am Main
• Project Head: Professor Dr. Michael Rother