Selenium-dependent gene regulation in Archaea

• Applicant: Professor Dr. Michael Rother
• Subject Area: Metabolism, Biochemistry and Genetics of Microorganisms
• Term: from 2019 to 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 422447039

Selenium is an essential trace element for many members of all three domains of life, but how selenium is transported into cells is unknown. Selenium exerts its biological function through the co-translationally inserted amino acid selenocysteine (Sec) and the tRNA modification 2-selenouridine (SeU). The methanogenic archaeon Methanococcus maripaludis employs Sec-containing proteins in its central energy metabolism, hydrogenotrophic methanogenesis. However, when selenium is scarce, a set of selenium-independent isoenzymes is induced, rendering growth independent of this trace element. However, how the cellular selenium status is sensed, and how this information is transduced to alter gene expression is unknown. Selenophosphate, which is the biosynthetic precursor of both Sec and SeU, is an attractive candidate for representing the cellular selenium status. Furthermore, phenotypic analyses of M. maripaludis mutants suggest involvement of the LysR-type transcription regulator HrsM in selenium-dependent activation of the selenoprotein genes and repression of the isogenes, but the mechanism of HrsM-dependent gene regulation is unknown. To elucidate how (and in what form) M. maripaludis transports selenium into the cell, to define the metabolic cue representing the cellular selenium status, and to unravel the mechanism HrsM either activates or represses gene expression in a selenium-dependent manner, is the aim of the proposed project.

• DFG Programme: Research Grants