Analysis of the Cellular Roles of MOCS3 Identifies a MOCS3-Independent Localization of NFS1 at the Tips of the Centrosome

Publication type:
Journal article
Metadata:
Autoren
  • Yannika Neukranz
  • Annika Kotter
  • Lena Beilschmidt
  • Zvonimir Marelja
  • Mark Helm
  • Ralph Graf
  • Silke Leimkuehler
Autoren-URL
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000463681600011&DestLinkType=FullRecord&DestApp=WOS_CPL
DOI
10.1021/acs.biochem.8b01160
Externe Identifier
  • Clarivate Analytics Document Solution ID: HS2HL
  • PubMed Identifier: 30817134
ISSN
0006-2960
Ausgabe der Veröffentlichung
13
Zeitschrift
BIOCHEMISTRY
Paginierung
1786 - 1798
Datum der Veröffentlichung
2019
Status
Published
Titel
Analysis of the Cellular Roles of MOCS3 Identifies a MOCS3-Independent Localization of NFS1 at the Tips of the Centrosome
Sub types
  • Article
Ausgabe der Zeitschrift
58

Data source: Web of Science (Lite)

Other metadata sources:
Autoren
  • Yannika Neukranz
  • Annika Kotter
  • Lena Beilschmidt
  • Zvonimir Marelja
  • Mark Helm
  • Ralph Gräf
  • Silke Leimkühler
DOI
10.1021/acs.biochem.8b01160
eISSN
1520-4995
ISSN
0006-2960
Ausgabe der Veröffentlichung
13
Zeitschrift
Biochemistry
Sprache
en
Online publication date
2019
Paginierung
1786 - 1798
Datum der Veröffentlichung
2019
Status
Published
Herausgeber
American Chemical Society (ACS)
Herausgeber URL
http://dx.doi.org/10.1021/acs.biochem.8b01160
Datum der Datenerfassung
2023
Titel
Analysis of the Cellular Roles of MOCS3 Identifies a MOCS3-Independent Localization of NFS1 at the Tips of the Centrosome
Ausgabe der Zeitschrift
58

Data source: Crossref

Abstract
The deficiency of the molybdenum cofactor (Moco) is an autosomal recessive disease, which leads to the loss of activity of all molybdoenzymes in humans with sulfite oxidase being the essential protein. Moco deficiency generally results in death in early childhood. Moco is a sulfur-containing cofactor synthesized in the cytosol with the sulfur being provided by a sulfur relay system composed of the l-cysteine desulfurase NFS1, MOCS3, and MOCS2A. Human MOCS3 is a dual-function protein that was shown to play an important role in Moco biosynthesis and in the mcm<sup>5</sup>s<sup>2</sup>U thio modifications of nucleosides in cytosolic tRNAs for Lys, Gln, and Glu. In this study, we constructed a homozygous MOCS3 knockout in HEK293T cells using the CRISPR/Cas9 system. The effects caused by the absence of MOCS3 were analyzed in detail. We show that sulfite oxidase activity was almost completely abolished, on the basis of the absence of Moco in these cells. In addition, mcm<sup>5</sup>s<sup>2</sup>U thio-modified tRNAs were not detectable. Because the l-cysteine desulfurase NFS1 was shown to act as a sulfur donor for MOCS3 in the cytosol, we additionally investigated the impact of a MOCS3 knockout on the cellular localization of NFS1. By different methods, we identified a MOCS3-independent novel localization of NFS1 at the centrosome.
Autoren
  • Yannika Neukranz
  • Annika Kotter
  • Lena Beilschmidt
  • Zvonimir Marelja
  • Mark Helm
  • Ralph Gräf
  • Silke Leimkühler
DOI
10.1021/acs.biochem.8b01160
eISSN
1520-4995
Externe Identifier
  • PubMed Identifier: 30817134
Funding acknowledgements
  • Max-Planck-Gesellschaft:
  • Deutsche Forschungsgemeinschaft: LE1171/9-2
Open access
false
ISSN
0006-2960
Ausgabe der Veröffentlichung
13
Zeitschrift
Biochemistry
Schlüsselwörter
  • Hela Cells
  • Centrosome
  • Humans
  • Pteridines
  • Coenzymes
  • Aconitate Hydratase
  • Carbon-Sulfur Lyases
  • Isocitrate Dehydrogenase
  • Nucleotidyltransferases
  • Sulfurtransferases
  • Metalloproteins
  • RNA, Transfer
  • Sulfite Oxidase
  • HEK293 Cells
  • CRISPR-Cas Systems
  • Molybdenum Cofactors
Sprache
eng
Medium
Print-Electronic
Online publication date
2019
Paginierung
1786 - 1798
Datum der Veröffentlichung
2019
Status
Published
Datum der Datenerfassung
2019
Titel
Analysis of the Cellular Roles of MOCS3 Identifies a MOCS3-Independent Localization of NFS1 at the Tips of the Centrosome.
Sub types
  • Research Support, Non-U.S. Gov't
  • Journal Article
Ausgabe der Zeitschrift
58

Data source: Europe PubMed Central

Abstract
The deficiency of the molybdenum cofactor (Moco) is an autosomal recessive disease, which leads to the loss of activity of all molybdoenzymes in humans with sulfite oxidase being the essential protein. Moco deficiency generally results in death in early childhood. Moco is a sulfur-containing cofactor synthesized in the cytosol with the sulfur being provided by a sulfur relay system composed of the l-cysteine desulfurase NFS1, MOCS3, and MOCS2A. Human MOCS3 is a dual-function protein that was shown to play an important role in Moco biosynthesis and in the mcm5s2U thio modifications of nucleosides in cytosolic tRNAs for Lys, Gln, and Glu. In this study, we constructed a homozygous MOCS3 knockout in HEK293T cells using the CRISPR/Cas9 system. The effects caused by the absence of MOCS3 were analyzed in detail. We show that sulfite oxidase activity was almost completely abolished, on the basis of the absence of Moco in these cells. In addition, mcm5s2U thio-modified tRNAs were not detectable. Because the l-cysteine desulfurase NFS1 was shown to act as a sulfur donor for MOCS3 in the cytosol, we additionally investigated the impact of a MOCS3 knockout on the cellular localization of NFS1. By different methods, we identified a MOCS3-independent novel localization of NFS1 at the centrosome.
Autoren
  • Yannika Neukranz
  • Annika Kotter
  • Lena Beilschmidt
  • Zvonimir Marelja
  • Mark Helm
  • Ralph Gräf
  • Silke Leimkühler
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/30817134
DOI
10.1021/acs.biochem.8b01160
eISSN
1520-4995
Ausgabe der Veröffentlichung
13
Zeitschrift
Biochemistry
Schlüsselwörter
  • Aconitate Hydratase
  • CRISPR-Cas Systems
  • Carbon-Sulfur Lyases
  • Centrosome
  • Coenzymes
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Isocitrate Dehydrogenase
  • Metalloproteins
  • Molybdenum Cofactors
  • Nucleotidyltransferases
  • Pteridines
  • RNA, Transfer
  • Sulfite Oxidase
  • Sulfurtransferases
Sprache
eng
Country
United States
Paginierung
1786 - 1798
Datum der Veröffentlichung
2019
Status
Published
Datum, an dem der Datensatz öffentlich gemacht wurde
2020
Titel
Analysis of the Cellular Roles of MOCS3 Identifies a MOCS3-Independent Localization of NFS1 at the Tips of the Centrosome.
Sub types
  • Journal Article
  • Research Support, Non-U.S. Gov't
Ausgabe der Zeitschrift
58

Data source: PubMed

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