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

Rościsław Krutyhołowa, Alexander Hammermeister, Rene Zabel (Lead / Corresponding author), Wael Abdel-Fattah, Annekathrin Reinhardt-Tews, Mark Helm, Michael J. R. Stark, Karin D. Breunig, Raffael Schaffrath, Sebastian Glatt

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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.

Original languageEnglish
Pages (from-to)4814-4830
Number of pages17
JournalNucleic Acids Research
Volume47
Issue number9
Early online date27 Mar 2019
DOIs
Publication statusPublished - 21 May 2019

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Transfer RNA
Adenosine Triphosphatases
Selenocysteine
Anticodon
Hydrolysis
Adenosine Triphosphate
Uridine
Hydrolases
Proteome
Eukaryota
Homeostasis
Phosphotransferases
Nucleotides
RNA
Proteins

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Krutyhołowa, R., Hammermeister, A., Zabel, R., Abdel-Fattah, W., Reinhardt-Tews, A., Helm, M., ... Glatt, S. (2019). Kti12, a PSTK-like tRNA dependent ATPase essential for tRNA modification by Elongator. Nucleic Acids Research, 47(9), 4814-4830. https://doi.org/10.1093/nar/gkz190
Krutyhołowa, Rościsław ; Hammermeister, Alexander ; Zabel, Rene ; Abdel-Fattah, Wael ; Reinhardt-Tews, Annekathrin ; Helm, Mark ; Stark, Michael J. R. ; Breunig, Karin D. ; Schaffrath, Raffael ; Glatt, Sebastian. / Kti12, a PSTK-like tRNA dependent ATPase essential for tRNA modification by Elongator. In: Nucleic Acids Research. 2019 ; Vol. 47, No. 9. pp. 4814-4830.
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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.",
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Krutyhołowa, R, Hammermeister, A, Zabel, R, Abdel-Fattah, W, Reinhardt-Tews, A, Helm, M, Stark, MJR, Breunig, KD, Schaffrath, R & Glatt, S 2019, 'Kti12, a PSTK-like tRNA dependent ATPase essential for tRNA modification by Elongator', Nucleic Acids Research, vol. 47, no. 9, pp. 4814-4830. https://doi.org/10.1093/nar/gkz190

Kti12, a PSTK-like tRNA dependent ATPase essential for tRNA modification by Elongator. / Krutyhołowa, Rościsław; Hammermeister, Alexander; Zabel, Rene (Lead / Corresponding author); Abdel-Fattah, Wael; Reinhardt-Tews, Annekathrin; Helm, Mark; Stark, Michael J. R.; Breunig, Karin D.; Schaffrath, Raffael; Glatt, Sebastian.

In: Nucleic Acids Research, Vol. 47, No. 9, 21.05.2019, p. 4814-4830.

Research output: Contribution to journalArticle

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AU - Hammermeister, Alexander

AU - Zabel, Rene

AU - Abdel-Fattah, Wael

AU - Reinhardt-Tews, Annekathrin

AU - Helm, Mark

AU - Stark, Michael J. R.

AU - Breunig, Karin D.

AU - Schaffrath, Raffael

AU - Glatt, Sebastian

N1 - OPUS10 grant [UMO-2015/19/B/NZ1/00343 to R.K. and S.G.] from the National Science Centre; TEAM TECH CORE FACILITY/2017–4/6 grant from Foundation for Polish Science (to S.G.), a joint research grant from the Biotechnology and Biological Sciences Research Council (BBSRC) [BB/F0191629/1 to M.J.R.S., BB/F019106/1 to R.S.]; Deutsche Forschungsgemeinschaft (DFG) [SCHA750/18 to to R.S., BR921/9 to K.D.B.]; Priority Program 1784 Chemical Biology of Native Nucleic Acid Modifications [HE3397/13 to to M.H., SCHA750/20 to R.S.]; research consortium PhosMOrg (P/1082: University of Kassel, Germany to R.S.]; STSM fellowship award (to A.H.) in the framework of the European Union Cost Action [EPITRAN CA16120]. Funding for open access charge: Narodowe Centrum Nauki [UMO-2015/19/B/NZ1/00343]; Deutsche Forschungsgemeinschaft [SCHA750/18].

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Krutyhołowa R, Hammermeister A, Zabel R, Abdel-Fattah W, Reinhardt-Tews A, Helm M et al. Kti12, a PSTK-like tRNA dependent ATPase essential for tRNA modification by Elongator. Nucleic Acids Research. 2019 May 21;47(9):4814-4830. https://doi.org/10.1093/nar/gkz190