A Moonlighting Human Protein Is Involved in Mitochondrial Import of tRNA.
In yeast Saccharomyces cerevisiae, ~3% of the lysine transfer RNA acceptor 1 (tRK1) pool is imported into mitochondria while the second isoacceptor, tRK2, fully remains in the cytosol. The mitochondrial function of tRK1 is suggested to boost mitochondrial translation under stress conditions. Strikingly, yeast tRK1 can also be imported into human mitochondria in vivo, and can thus be potentially used as a vector to address RNAs with therapeutic anti-replicative capacity into mitochondria of sick cells. Better understanding of the targeting mechanism in yeast and human is thus critical. Mitochondrial import of tRK1 in yeast proceeds first through a drastic conformational rearrangement of tRK1 induced by enolase 2, which carries this freight to the mitochondrial pre-lysyl-tRNA synthetase (preMSK). The latter may cross the mitochondrial membranes to reach the matrix where imported tRK1 could be used by the mitochondrial translation apparatus. This work focuses on the characterization of the complex that tRK1 forms with human enolases and their role on the interaction between tRK1 and human pre-lysyl-tRNA synthetase (preKARS2).
Department of Molecular and Cellular Genetics, UMR 7156 Génétique Moléculaire, Génomique, Microbiologie (GMGM), CNRS-Université de Strasbourg, 67084 Strasbourg, France. piotr.kamenski@gmail.com.|Department of Molecular Biology, Biology Faculty of Moscow State University, 119992 Moscow, Russia. piotr.kamenski@gmail.com.
Maria
M
Baleva
Department of Molecular and Cellular Genetics, UMR 7156 Génétique Moléculaire, Génomique, Microbiologie (GMGM), CNRS-Université de Strasbourg, 67084 Strasbourg, France. qureishi83@gmail.com.
Ali
A
Gowher
Department of Molecular Biology, Biology Faculty of Moscow State University, 119992 Moscow, Russia. piotr.kamenski@gmail.com.
Piotr
P
Kamenski
Department of Molecular and Cellular Genetics, UMR 7156 Génétique Moléculaire, Génomique, Microbiologie (GMGM), CNRS-Université de Strasbourg, 67084 Strasbourg, France. i.tarassov@unistra.fr.
Ivan
I
Tarassov
Department of Molecular and Cellular Genetics, UMR 7156 Génétique Moléculaire, Génomique, Microbiologie (GMGM), CNRS-Université de Strasbourg, 67084 Strasbourg, France. n.entelis@unistra.fr.
Nina
N
Entelis
Department of Molecular and Cellular Genetics, UMR 7156 Génétique Moléculaire, Génomique, Microbiologie (GMGM), CNRS-Université de Strasbourg, 67084 Strasbourg, France. b.masquida@unistra.fr.
Benoît
B
Masquida
D000465:Algorithms; D000595:Amino Acid Sequence; D001483:Base Sequence; D001692:Biological Transport; D027682:Cation Transport Proteins / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D030562:Databases, Protein; D056945:Hep G2 Cells; D006801:Humans; D008250:Lysine-tRNA Ligase / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D010751:Phosphopyruvate Hydratase / Q000378:metabolism*; D014176:Protein Biosynthesis; D011487:Protein Conformation; D012343:RNA, Transfer / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
D027682:Cation Transport Proteins; D029701:Saccharomyces cerevisiae Proteins; C068664:TRK1 protein, S cerevisiae; D012343:RNA, Transfer; D010751:Phosphopyruvate Hydratase; D008250:Lysine-tRNA Ligase