Kti12, a PSTK-like tRNA dependent ATPase essential for tRNA modification by Elongator

Autoren

Rościsław Krutyhołowa
Alexander Hammermeister
Rene Zabel
Wael Abdel-Fattah
Annekathrin Reinhardt-Tews
Mark Helm
Michael JR Stark
Karin D Breunig
Raffael Schaffrath
Sebastian Glatt

DOI

10.1093/nar/gkz190

eISSN

1362-4962

ISSN

0305-1048

Ausgabe der Veröffentlichung

9

Zeitschrift

Nucleic Acids Research

Sprache

en

Online publication date

2019

Paginierung

4814 - 4830

Datum der Veröffentlichung

2019

Status

Published

Herausgeber

Oxford University Press (OUP)

Herausgeber URL

http://dx.doi.org/10.1093/nar/gkz190

Datum der Datenerfassung

2022

Titel

Kti12, a PSTK-like tRNA dependent ATPase essential for tRNA modification by Elongator

Ausgabe der Zeitschrift

47

Datenquelle: Crossref

Abstract

Posttranscriptional RNA modifications occur in all domains of life. Modifications of anticodon bases are of particular importance for ribosomal decoding and proteome homeostasis. The Elongator complex modifies uridines in the wobble position and is highly conserved in eukaryotes. Despite recent insights into Elongator's architecture, the structure and function of its regulatory factor Kti12 have remained elusive. Here, we present the crystal structure of Kti12's nucleotide hydrolase domain trapped in a transition state of ATP hydrolysis. The structure reveals striking similarities to an O-phosphoseryl-tRNA kinase involved in the selenocysteine pathway. Both proteins employ similar mechanisms of tRNA binding and show tRNASec-dependent ATPase activity. In addition, we demonstrate that Kti12 binds directly to Elongator and that ATP hydrolysis is crucial for Elongator to maintain proper tRNA anticodon modification levels in vivo. In summary, our data reveal a hitherto uncharacterized link between two translational control pathways that regulate selenocysteine incorporation and affect ribosomal tRNA selection via specific tRNA modifications.

Addresses

Max Planck Research Group at the Malopolska Centre of Biotechnology, Jagiellonian University, Krakow, Poland.

Autoren

Rościsław Krutyhołowa
Alexander Hammermeister
Rene Zabel
Wael Abdel-Fattah
Annekathrin Reinhardt-Tews
Mark Helm
Michael JR Stark
Karin D Breunig
Raffael Schaffrath
Sebastian Glatt

DOI

10.1093/nar/gkz190

eISSN

1362-4962

Externe Identifier

PubMed Identifier: 30916349
PubMed Central ID: PMC6511879

Funding acknowledgements

National Science Centre: UMO-2015/19/B/NZ1/00343
Biotechnology and Biological Sciences Research Council: BB/F019106/1
Biotechnology and Biological Sciences Research Council: BB/F0191629/1

Open access

true

ISSN

0305-1048

Ausgabe der Veröffentlichung

9

Zeitschrift

Nucleic acids research

Schlüsselwörter

Ribosomes
Saccharomyces cerevisiae
Chaetomium
Adaptor Proteins, Signal Transducing
Carrier Proteins
Saccharomyces cerevisiae Proteins
RNA, Transfer
Anticodon
Uridine
Crystallography, X-Ray
RNA Processing, Post-Transcriptional
Protein Conformation
Adenosine Triphosphatases

Sprache

eng

Medium

Print

Open access status

Open Access

Paginierung

4814 - 4830

Datum der Veröffentlichung

2019

Status

Published

Publisher licence

CC BY-NC

Datum der Datenerfassung

2019

Titel

Kti12, a PSTK-like tRNA dependent ATPase essential for tRNA modification by Elongator.

Sub types

Research Support, Non-U.S. Gov't
research-article
Journal Article

Ausgabe der Zeitschrift

47

Files

https://europepmc.org/articles/PMC6511879?pdf=render

Datenquelle: Europe PubMed Central

Abstract

Posttranscriptional RNA modifications occur in all domains of life. Modifications of anticodon bases are of particular importance for ribosomal decoding and proteome homeostasis. The Elongator complex modifies uridines in the wobble position and is highly conserved in eukaryotes. Despite recent insights into Elongator's architecture, the structure and function of its regulatory factor Kti12 have remained elusive. Here, we present the crystal structure of Kti12's nucleotide hydrolase domain trapped in a transition state of ATP hydrolysis. The structure reveals striking similarities to an O-phosphoseryl-tRNA kinase involved in the selenocysteine pathway. Both proteins employ similar mechanisms of tRNA binding and show tRNASec-dependent ATPase activity. In addition, we demonstrate that Kti12 binds directly to Elongator and that ATP hydrolysis is crucial for Elongator to maintain proper tRNA anticodon modification levels in vivo. In summary, our data reveal a hitherto uncharacterized link between two translational control pathways that regulate selenocysteine incorporation and affect ribosomal tRNA selection via specific tRNA modifications.

Date of acceptance

2019

Autoren

Rościsław Krutyhołowa
Alexander Hammermeister
Rene Zabel
Wael Abdel-Fattah
Annekathrin Reinhardt-Tews
Mark Helm
Michael JR Stark
Karin D Breunig
Raffael Schaffrath
Sebastian Glatt

Autoren-URL

https://www.ncbi.nlm.nih.gov/pubmed/30916349

DOI

10.1093/nar/gkz190

eISSN

1362-4962

Externe Identifier

PubMed Central ID: PMC6511879

Funding acknowledgements

Biotechnology and Biological Sciences Research Council: BB/F019106/1

Ausgabe der Veröffentlichung

9

Zeitschrift

Nucleic Acids Res

Schlüsselwörter

Adaptor Proteins, Signal Transducing
Adenosine Triphosphatases
Anticodon
Carrier Proteins
Chaetomium
Crystallography, X-Ray
Protein Conformation
RNA Processing, Post-Transcriptional
RNA, Transfer
Ribosomes
Saccharomyces cerevisiae
Saccharomyces cerevisiae Proteins
Uridine

Sprache

eng

Country

England

Paginierung

4814 - 4830

PII

5420542

Datum der Veröffentlichung

2019

Status

Published

Datum, an dem der Datensatz öffentlich gemacht wurde

2019

Titel

Kti12, a PSTK-like tRNA dependent ATPase essential for tRNA modification by Elongator.

Sub types

Journal Article
Research Support, Non-U.S. Gov't

Ausgabe der Zeitschrift

47

Datenquelle: PubMed

Kti12, a PSTK-like tRNA dependent ATPase essential for tRNA modification by Elongator

Files

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