TY - JOUR
T1 - Kti12, a PSTK-like tRNA dependent ATPase essential for tRNA modification by Elongator
AU - Krutyhołowa, Rościsław
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].
PY - 2019/5/21
Y1 - 2019/5/21
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85066056270&partnerID=8YFLogxK
U2 - 10.1093/nar/gkz190
DO - 10.1093/nar/gkz190
M3 - Article
C2 - 30916349
SN - 0305-1048
VL - 47
SP - 4814
EP - 4830
JO - Nucleic Acids Research
JF - Nucleic Acids Research
IS - 9
ER -