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

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

doi:10.1038/nature07643

Cited by 253 publications

(365 citation statements)

References 48 publications

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“…The carboxyl group of the C-terminal glycine of Urm1 is modified to a thiocarboxylate by the addition of sulfur (9,10,12,13). Thiocarboxylated Urm1 functions as a sulfur donor in tRNA thiolation (9)(10)(11)(12)(13).…”

Section: Discussionmentioning

confidence: 99%

“…Thiocarboxylated Urm1 functions as a sulfur donor in tRNA thiolation (9)(10)(11)(12)(13). The consequences of thiocarboxylation on the ability of Urm1 to form protein conjugates have not been explored until now.…”

Section: Discussionmentioning

confidence: 99%

“…Next, MOCS3 adenylates the C terminus of Urm1, followed by the transfer of sulfur to the terminal glycine of Urm1 (15). Urm1 associates with the thiouridylases ATPBD3 (also known as CTU1 in Homo sapiens and Ncs6p in S. cerevisiae) and CTU2 (Ncs2p in S. cerevisiae), which mediate the thiolation of wobble uridines in tRNA Lys(UUU) , tRNA Gln(UUG) , and tRNA Glu(UUC) (9)(10)(11)(12)(13)(16)(17)(18).…”

mentioning

confidence: 99%

“…MoaD and ThiS are thiocarboxylated at their C terminus and serve as sulfur donors in molybdopterin and thiamine synthesis, respectively (8). Urm1 is also thiocarboxylated and functions as a sulfur donor in tRNA thiolation in Saccharomyces cerevisiae and mammalian cells, thus resembling prokaryotic sulfur carriers (9)(10)(11)(12)(13).…”

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confidence: 99%

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Role of the ubiquitin-like protein Urm1 as a noncanonical lysine-directed protein modifier

Veen

Schorpp

Schlieker

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

171

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The ubiquitin (Ub)-related modifier Urm1 functions as a sulfur carrier in tRNA thiolation by means of a mechanism that requires the formation of a thiocarboxylate at the C-terminal glycine residue of Urm1. However, whether Urm1 plays an additional role as a Ublike protein modifier remains unclear. Here, we show that Urm1 is conjugated to lysine residues of target proteins and that oxidative stress enhances protein urmylation in both Saccharomyces cerevisiae and mammalian cells. Similar to ubiquitylation, urmylation involves a thioester intermediate and results in the formation of a covalent peptide bond between Urm1 and its substrates. In contrast to modification by canonical Ub-like modifiers, however, conjugation of Urm1 involves a C-terminal thiocarboxylate of the modifier. We have confirmed that the peroxiredoxin Ahp1 is such a substrate in S. cerevisiae and found that Urm1 targets a specific lysine residue of Ahp1 in vivo. In addition, we have identified several unique substrates in mammalian cells and show that Urm1 targets at least two pathways on oxidant treatment. First, Urm1 is appended to lysine residues of three components that function in its own pathway (i.e., MOCS3, ATPBD3, and CTU2). Second, Urm1 is conjugated to the nucleocytoplasmic shuttling factor cellular apoptosis susceptibility protein. Thus, Urm1 has a conserved dual role by integrating the functions of prokaryotic sulfur carriers with those of eukaryotic protein modifiers of the Ub family.posttranslational modification | hydrogen peroxide | nuclear transport | Uba4 | USP15

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Role of the ubiquitin-like protein Urm1 as a noncanonical lysine-directed protein modifier

Veen

Schorpp

Schlieker

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

171

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“…Thus, these observations suggest that Urm1 activation is more similar to that of a prokaryotic sulfur carrier protein than that of a UBL. This function has been linked to the downstream thiolation of certain tRNAs during oxidative stress, where their modification alters their decoding specificity (16)(17)(18)(19).…”

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confidence: 99%

Urm1 couples sulfur transfer to ubiquitin-like protein function in oxidative stress

Petroski¹,

Salvesen

Wolf³

2011

Proc. Natl. Acad. Sci. U.S.A.

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Identification of a rhodanese‐like protein involved in thiouridine biosynthesis in Thermus thermophilus tRNA

2016

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Incorporation of a sulfur atom into 2-thioribothymidine (s T or 5-methyl-2-thiouridine) at position 54 in thermophile tRNA is accomplished by an elaborate system composed of many proteins which confers thermostability to the translation system. We identified ttuD (tRNA-two-thiouridine D) as a gene for the synthesis of s T54 in Thermus thermophilus. The rhodanese-like protein TtuD enhances the activity of cysteine desulfurases and receives the persulfide generated by cysteine desulfurases in vitro. TtuD also enhances the formation of thiocarboxylated TtuB, the sulfur donor for the tRNA sulfurtransferase TtuA. Since cysteine desulfurases are the first enzymes in the synthesis of s T and other sulfur-containing compounds, TtuD has a role to direct sulfur flow to s T synthesis.

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

Cited by 253 publications

References 48 publications

Role of the ubiquitin-like protein Urm1 as a noncanonical lysine-directed protein modifier

Role of the ubiquitin-like protein Urm1 as a noncanonical lysine-directed protein modifier

Urm1 couples sulfur transfer to ubiquitin-like protein function in oxidative stress

Identification of a rhodanese‐like protein involved in thiouridine biosynthesis in Thermus thermophilus tRNA

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