Ubiquitin-related modifier Urm1 acts as a sulphur carrier in thiolation of eukaryotic transfer RNA

Sebastian Leidel, Patrick G. A. Pedrioli, Tamara Bucher, Renee Brost, Michael Costanzo, Alexander Schmidt, Ruedi Aebersold, Charles Boone, Kay Hofmann, Matthias Peter

    Research output: Contribution to journalArticlepeer-review

    184 Citations (Scopus)

    Abstract

    Ubiquitin-like proteins (UBLs) can change protein function, localization or turnover by covalent attachment to lysine residues(1). Although UBLs achieve this conjugation through an intricate enzymatic cascade, their bacterial counterparts MoaD and ThiS function as sulphur carrier proteins(2,3). Here we show that Urm1p, the most ancient UBL3, acts as a sulphur carrier in the process of eukaryotic transfer RNA ( tRNA) modification, providing a possible evolutionary link between UBL and sulphur transfer. Moreover, we identify Uba4p, Ncs2p, Ncs6p and Yor251cp as components of this conserved pathway. Using in vitro assays, we show that Ncs6p binds to tRNA, whereas Uba4p first adenylates and then directly transfers sulphur onto Urm1p. Finally, functional analysis reveals that the thiolation function of Urm1p is critical to regulate cellular responses to nutrient starvation and oxidative stress conditions, most likely by increasing translation fidelity.

    Original languageEnglish
    Pages (from-to)228-U9
    Number of pages6
    JournalNature
    Volume458
    Issue number7235
    DOIs
    Publication statusPublished - 12 Mar 2009

    Cite this