title: Ubiquitin-related modifier Urm1 acts as a sulphur carrier in thiolation of eukaryotic transfer RNA.
abstract: Ubiquitin-like proteins (UBLs) can change protein function, localization or turnover by covalent attachment to lysine residues. Although UBLs achieve this conjugation through an intricate enzymatic cascade, their bacterial counterparts MoaD and ThiS function as sulphur carrier proteins. Here we show that Urm1p, the most ancient UBL, 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.
authors.affiliation: Institute of Biochemistry, ETH Zurich, Schafmattstrasse 18, CH-8093 Zurich, Switzerland.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Leidel
authors.forename: Patrick G A
authors.initials: PG
authors.lastname: Pedrioli
authors.forename: Tamara
authors.initials: T
authors.lastname: Bucher
authors.forename: Renée
authors.initials: R
authors.lastname: Brost
authors.forename: Michael
authors.initials: M
authors.lastname: Costanzo
authors.forename: Alexander
authors.initials: A
authors.lastname: Schmidt
authors.forename: Ruedi
authors.initials: R
authors.lastname: Aebersold
authors.forename: Charles
authors.initials: C
authors.lastname: Boone
authors.forename: Kay
authors.initials: K
authors.lastname: Hofmann
authors.forename: Matthias
authors.initials: M
authors.lastname: Peter
mesh_terms: D005057:Eukaryotic Cells / Q000378:metabolism*; D012343:RNA, Transfer / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000378:metabolism / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D013455:Sulfur / Q000378:metabolism*
chemical_list: D029701:Saccharomyces cerevisiae Proteins; C406282:URM1 protein, S cerevisiae; D013455:Sulfur; D012343:RNA, Transfer