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Binding to G-quadruplex RNA activates the mitochondrial GTPase NOA1
Authors:Natalie Al-Furoukh  Steffi Goffart  Marten Szibor  Sjoerd Wanrooij  Thomas Braun
Affiliation:1. Max-Planck-Institute for Heart and Lung Research, Ludwigstrasse 43, 61231 Bad Nauheim, Germany;2. University of Eastern Finland, Department of Biology, Yliopistokatu 7, 80101 Joensuu, Finland;3. University of Gothenburg, Department of Medical Biochemistry and Cell Biology, Box 440, SE-40530, Göteborg, Sweden;4. Burgers Lab, Department of Biochemistry and Biophysics, Washington University, Campus Box 8231, 4566 Scott Avenue, MO 63110, St. Louis, USA
Abstract:NOA1 is an evolutionary conserved, nuclear encoded GTPase essential for mitochondrial function and cellular survival. The function of NOA1 for assembly of mitochondrial ribosomes and regulation of OXPHOS activity depends on its GTPase activity, but so far no ligands have been identified that regulate the GTPase activity of NOA1. To identify nucleic acids that bind to the RNA-binding domain of NOA1 we employed SELEX (Systemic Evolution of Ligands by EXponential Enrichment) using recombinant mouse wildtype NOA1 and the GTPase mutant NOA1-K353R. We found that NOA1 binds specifically to oligonucleotides that fold into guanine tetrads (G-quadruplexes). Binding of G-quadruplex oligonucleotides stimulated the GTPase activity of NOA1 suggesting a regulatory link between G-quadruplex containing RNAs, NOA1 function and assembly of mitochondrial ribosomes.
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