Binding to G-quadruplex RNA activates the mitochondrial GTPase NOA1.
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.
Max-Planck-Institute for Heart and Lung Research, Ludwigstrasse 43, 61231 Bad Nauheim, Germany. Electronic address: Natalie.al-furoukh@mpi-bn.mpg.de.
Natalie
N
Al-Furoukh
Max-Planck-Institute for Heart and Lung Research, Ludwigstrasse 43, 61231 Bad Nauheim, Germany; University of Eastern Finland, Department of Biology, Yliopistokatu 7, 80101 Joensuu, Finland. Electronic address: Steffi.goffart@uef.fi.
Steffi
S
Goffart
Max-Planck-Institute for Heart and Lung Research, Ludwigstrasse 43, 61231 Bad Nauheim, Germany. Electronic address: Marten.szibor@mpi-bn.mpg.de.
Marten
M
Szibor
University of Gothenburg, Department of Medical Biochemistry and Cell Biology, Box 440, SE-40530, Göteborg, Sweden; Burgers Lab, Department of Biochemistry and Biophysics, Washington University, Campus Box 8231, 4566 Scott Avenue, MO 63110, St. Louis, USA. Electronic address: Sjoerd.wanrooij@medkem.gu.se.
Sjoerd
S
Wanrooij
Max-Planck-Institute for Heart and Lung Research, Ludwigstrasse 43, 61231 Bad Nauheim, Germany. Electronic address: thomas.braun@mpi-bn.mpg.de.
Thomas
T
Braun
D000818:Animals; D001120:Arginine / Q000378:metabolism; D001483:Base Sequence; D004789:Enzyme Activation; D054856:G-Quadruplexes; D020558:GTP Phosphohydrolases / Q000302:isolation & purification / Q000378:metabolism*; D006868:Hydrolysis; D008239:Lysine / Q000378:metabolism; D051379:Mice; D008928:Mitochondria / Q000201:enzymology*; D050505:Mutant Proteins / Q000302:isolation & purification / Q000378:metabolism; D011485:Protein Binding; D012313:RNA / Q000737:chemistry* / Q000378:metabolism*; D012335:RNA, Ribosomal / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D052156:SELEX Aptamer Technique; D013379:Substrate Specificity
D050505:Mutant Proteins; D012335:RNA, Ribosomal; C075526:RNA, ribosomal, 12S; D011994:Recombinant Proteins; D012313:RNA; D001120:Arginine; D020558:GTP Phosphohydrolases; C559566:NOA1 protein, mouse; D008239:Lysine
Aptamer; Binding motif; G-quadruplex; GTPase; NOA1; Nitric Oxide Associated 1; OXPHOS; SELEX; Systemic Evolution of Ligands by Exponential Enrichment; UTR; double stranded; ds; oxidative phosphorylation; single stranded; ss; untranslated region