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Same but different — Molecular comparison of human KTI12 and PSTK

Kti12 and PSTK are closely related and highly similar proteins implicated in different aspects of tRNA metabolism. Kti12 has been identified as an essential regulatory factor of the Elongator complex, involved in the modification of uridine bases in eukaryotic tRNAs. PSTK phosphorylates the tRNASec-...

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Published in:Biochimica et biophysica acta. Molecular cell research 2021-04, Vol.1868 (4), p.118945-118945, Article 118945
Main Authors: Smejda, Marta, Kądziołka, Dominika, Radczuk, Natalia, Krutyhołowa, Rościsław, Chramiec-Głąbik, Andrzej, Kędracka-Krok, Sylwia, Jankowska, Urszula, Biela, Anna, Glatt, Sebastian
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Language:English
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Summary:Kti12 and PSTK are closely related and highly similar proteins implicated in different aspects of tRNA metabolism. Kti12 has been identified as an essential regulatory factor of the Elongator complex, involved in the modification of uridine bases in eukaryotic tRNAs. PSTK phosphorylates the tRNASec-bound amino acid serine, which is required to synthesize selenocysteine. Kti12 and PSTK have previously been studied independently in various organisms, but only appear simultaneously in some animalia, including humans. As Kti12- and PSTK-related pathways are clinically relevant, it is of prime importance to understand their biological functions and mutual relationship in humans. Here, we use different tRNA substrates to directly compare the enzymatic activities of purified human KTI12 and human PSTK proteins. Our complementary Co-IP and BioID2 approaches in human cells confirm that Elongator is the main interaction partner of KTI12 but additionally indicate potential links to proteins involved in vesicular transport, RNA metabolism and deubiquitination. Moreover, we identify and validate a yet uncharacterized interaction between PSTK and γ-taxilin. Foremost, we demonstrate that human KTI12 and PSTK do not share interactors or influence their respective biological functions. Our data provide a comprehensive analysis of the regulatory networks controlling the activity of the human Elongator complex and selenocysteine biosynthesis. •KTI12 and PSTK, are expressed simultaneously only in animal cells.•Human KTI12 and PSTK show different substrate selectivity and reaction states in vitro.•Human KTI12 and PSTK can be linked to various cellular activities outside their genuine functions in tRNA metabolism.•The cellular interaction networks and of human KTI12 and PSTK are separated.
ISSN:0167-4889
1879-2596
DOI:10.1016/j.bbamcr.2020.118945