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Review
. 2008 Dec;9(12):1196-202.
doi: 10.1038/embor.2008.209.

Urm1 at the crossroad of modifications. 'Protein Modifications: Beyond the Usual Suspects' Review Series

Patrick G A Pedrioli  1 , Sebastian Leidel, Kay Hofmann
Affiliations
Review

Urm1 at the crossroad of modifications. 'Protein Modifications: Beyond the Usual Suspects' Review Series

Patrick G A Pedrioli et al. EMBO Rep. 2008 Dec.

Abstract

The ubiquitin-like protein Urm1 can be covalently conjugated to other proteins, such as the yeast thioredoxin peroxidase protein Ahp1p, through a mechanism involving the ubiquitin E1-like enzyme Uba4. Recent findings have revealed a second function of Urm1 as a sulphur carrier in the thiolation of eukaryotic cytoplasmic transfer RNAs (tRNAs). Interestingly, this new role of Urm1 is similar to the sulphur-carrier activity of its prokaryotic counterparts, strengthening the hypothesis that Urm1 is a molecular fossil of the ubiquitin-like protein family. Here, we discuss the function of Urm1 in light of its dual role in protein and RNA modification.

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Figures

Figure 1
Figure 1. Multiple sequence alignment and phylogenetic trees of ubiquitin-like proteins and their E1 enzymes.
(A) Nuclear magnetic-resonance structures of ubiquitin (Protein Data Bank identifier 1ubq) and Urm1 (Protein Data Bank identifier 2ax5). (B) Alignment of representative ubiquitin-like modifiers. With the exceptions of Urm1p (Saccharomyces cerevisiae), MoaD (Escherichia coli) and ThiS (E. coli), only human versions are shown. For the two-domain modifiers ISG15 and FAT10, only the relevant carboxy-terminal domain is shown. (C) Alignment of representative E1 enzymes that activate the modifiers shown in (B). Only the catalytically active ThiF domain is shown. (D) Neighbour-joining dendrogram of UBL modifiers derived from the alignment in (B). (E) Neighbour-joining dendrogram of E1 enzymes derived from the alignment in (C). FAT10, factor activated by TNF-α 10; ISG15, interferon-stimulated gene 15; MOCS2, molybdopterin cofactor synthesis gene 2; NEDD8, neural precursor cell expressed, developmentally down-regulated gene 8; SUMO, small ubiquitin-like modifier; Ub, ubiquitin; UBL, ubiquitin-like protein; UFM1, ubiquitin-fold modifier 1; URM1, ubiquitin-related modifier 1.
Figure 2
Figure 2. Similarities and differences between the ubiquitin, ThiS and Urm1 systems.
(A) The ubiquitin (Ubi) pathway is responsible for protein modification. (B) The ThiS pathway is responsible for the biosynthesis of thiamine. (C) The Urm1 pathway is responsible for protein and transfer RNA (tRNA) modification. The initial steps of all three pathways are similar, and require the activation of the ubiquitin-like molecule by acyl adenylation of its carboxyl terminus and formation of a covalent complex with the activating enzyme (through either an acyl disulphide or a thioester bond); however, the subsequent steps of the reaction mechanisms differ.
Figure 3
Figure 3. The URM1 pathway involved in the modification of transfer RNA bases.
(A) Uridine and mcm5s2U34. The ELP complex is responsible for the mcm5U34 modification, whereas the URM1 pathway is responsible for the thiolation (s2U34). (B) Overview of the molecules and reactions responsible for tRNA s2U34 formation. ELP, elongator protein; mcm5s2U34, 5-methoxy-carbonyl-methyl-2-thiouridine; mcm5U34, methoxy-carbonyl-methyl-uridine; s2U34, 2-thiouridine; tRNA, transfer RNA; URM1, ubiquitin-related modifier 1.
None
Patrick G.A. Pedrioli
None
Sebastian Leidel
None
Kay Hofmann
See this image and copyright information in PMC

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