Sulfur transfer and activation by ubiquitin-like modifier system Uba4•Urm1 link protein urmylation and tRNA thiolation in yeast

Publikationstyp:
Zeitschriftenaufsatz
Metadaten:
Autoren
  • Andre Juedes
  • Alexander Bruch
  • Roland Klassen
  • Mark Helm
  • Raffael Schaffrath
DOI
10.15698/mic2016.11.539
eISSN
2311-2638
Ausgabe der Veröffentlichung
11
Zeitschrift
Microbial Cell
Online publication date
2016
Paginierung
554 - 564
Status
Published online
Herausgeber
Shared Science Publishers OG
Herausgeber URL
http://dx.doi.org/10.15698/mic2016.11.539
Datum der Datenerfassung
2018
Titel
Sulfur transfer and activation by ubiquitin-like modifier system Uba4•Urm1 link protein urmylation and tRNA thiolation in yeast
Ausgabe der Zeitschrift
3

Datenquelle: Crossref

Andere Metadatenquellen:
Abstract
Urm1 is a unique dual-function member of the ubiquitin protein family and conserved from yeast to man. It acts both as a protein modifier in ubiquitin-like urmylation and as a sulfur donor for tRNA thiolation, which in concert with the Elongator pathway forms 5-methoxy-carbonyl-methyl-2-thio (mcm<sup>5</sup>s<sup>2</sup>) modified wobble uridines (U34) in anticodons. Using <i>Saccharomyces cerevisiae</i> as a model to study a relationship between these two functions, we examined whether cultivation temperature and sulfur supply previously implicated in the tRNA thiolation branch of the <i>URM1</i> pathway also contribute to proper urmylation. Monitoring Urm1 conjugation, we found urmylation of the peroxiredoxin Ahp1 is suppressed either at elevated cultivation temperatures or under sulfur starvation. In line with this, mutants with sulfur transfer defects that are linked to enzymes (Tum1, Uba4) required for Urm1 activation by thiocarboxylation (Urm1-COSH) were found to maintain drastically reduced levels of Ahp1 urmylation and mcm<sup>5</sup>s<sup>2</sup>U34 modification. Moreover, as revealed by site specific mutagenesis, the S-transfer rhodanese domain (RHD) in the E1-like activator (Uba4) crucial for Urm1-COSH formation is critical but not essential for protein urmylation and tRNA thiolation. In sum, sulfur supply, transfer and activation chemically link protein urmylation and tRNA thiolation. These are features that distinguish the ubiquitin-like modifier system Uba4•Urm1 from canonical ubiquitin family members and will help elucidate whether, in addition to their mechanistic links, the protein and tRNA modification branches of the <i>URM1</i> pathway may also relate in function to one another.
Addresses
  • Universität Kassel, Institut für Biologie, FG Mikrobiologie, Heinrich-Plett-Str. 40, 34132 Kassel, Germany.
Autoren
  • André Jüdes
  • Alexander Bruch
  • Roland Klassen
  • Mark Helm
  • Raffael Schaffrath
DOI
10.15698/mic2016.11.539
eISSN
2311-2638
Externe Identifier
  • PubMed Identifier: 28357324
  • PubMed Central ID: PMC5349211
Open access
true
ISSN
2311-2638
Ausgabe der Veröffentlichung
11
Zeitschrift
Microbial cell (Graz, Austria)
Sprache
eng
Medium
Electronic
Online publication date
2016
Open access status
Open Access
Paginierung
554 - 564
Datum der Veröffentlichung
2016
Status
Published
Publisher licence
CC BY
Datum der Datenerfassung
2017
Titel
Sulfur transfer and activation by ubiquitin-like modifier system Uba4•Urm1 link protein urmylation and tRNA thiolation in yeast.
Sub types
  • research-article
  • Journal Article
Ausgabe der Zeitschrift
3

Files

http://microbialcell.com/wordpress/wp-content/uploads/2016/10/2016A-Juedes-Microbial-Cell.pdf https://europepmc.org/articles/PMC5349211?pdf=render

Datenquelle: Europe PubMed Central

Abstract
Urm1 is a unique dual-function member of the ubiquitin protein family and conserved from yeast to man. It acts both as a protein modifier in ubiquitin-like urmylation and as a sulfur donor for tRNA thiolation, which in concert with the Elongator pathway forms 5-methoxy-carbonyl-methyl-2-thio (mcm5s2) modified wobble uridines (U34) in anticodons. Using Saccharomyces cerevisiae as a model to study a relationship between these two functions, we examined whether cultivation temperature and sulfur supply previously implicated in the tRNA thiolation branch of the URM1 pathway also contribute to proper urmylation. Monitoring Urm1 conjugation, we found urmylation of the peroxiredoxin Ahp1 is suppressed either at elevated cultivation temperatures or under sulfur starvation. In line with this, mutants with sulfur transfer defects that are linked to enzymes (Tum1, Uba4) required for Urm1 activation by thiocarboxylation (Urm1-COSH) were found to maintain drastically reduced levels of Ahp1 urmylation and mcm5s2U34 modification. Moreover, as revealed by site specific mutagenesis, the S-transfer rhodanese domain (RHD) in the E1-like activator (Uba4) crucial for Urm1-COSH formation is critical but not essential for protein urmylation and tRNA thiolation. In sum, sulfur supply, transfer and activation chemically link protein urmylation and tRNA thiolation. These are features that distinguish the ubiquitin-like modifier system Uba4•Urm1 from canonical ubiquitin family members and will help elucidate whether, in addition to their mechanistic links, the protein and tRNA modification branches of the URM1 pathway may also relate in function to one another.
Autoren
  • André Jüdes
  • Alexander Bruch
  • Roland Klassen
  • Mark Helm
  • Raffael Schaffrath
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/28357324
DOI
10.15698/mic2016.11.539
Externe Identifier
  • PubMed Central ID: PMC5349211
ISSN
2311-2638
Ausgabe der Veröffentlichung
11
Zeitschrift
Microb Cell
Schlüsselwörter
  • E1-like enzyme Uba4
  • Saccharomyces cerevisiae
  • protein urmylation
  • sulfur transferase Tum1
  • tRNA thiolation
  • tRNase zymocin
  • ubiquitin-like modifier Urm1
Sprache
eng
Country
Austria
Paginierung
554 - 564
PII
MIC0176E184
Datum der Veröffentlichung
2016
Status
Published online
Titel
Sulfur transfer and activation by ubiquitin-like modifier system Uba4•Urm1 link protein urmylation and tRNA thiolation in yeast.
Sub types
  • Journal Article
Ausgabe der Zeitschrift
3

Datenquelle: PubMed

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