Baleva Maria, Gowher Ali, Kamenski Piotr, Tarassov Ivan, Entelis Nina, Masquida Benoît
Department of Molecular and Cellular Genetics, UMR 7156 Génétique Moléculaire, Génomique, Microbiologie (GMGM), CNRS-Université de Strasbourg, 67084 Strasbourg, France.
Department of Molecular Biology, Biology Faculty of Moscow State University, 119992 Moscow, Russia.
Int J Mol Sci. 2015 Apr 24;16(5):9354-67. doi: 10.3390/ijms16059354.
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).
在酿酒酵母中，约3%的赖氨酸转运RNA受体1（tRK1）会被导入线粒体，而另一种同功受体tRK2则完全保留在细胞质中。tRK1的线粒体功能被认为是在应激条件下促进线粒体翻译。引人注目的是，酵母tRK1在体内也能被导入人类线粒体，因此有可能被用作载体，将具有治疗性抗复制能力的RNA导入病变细胞的线粒体中。因此，更好地理解酵母和人类中的靶向机制至关重要。酵母中tRK1的线粒体导入首先通过烯醇化酶2诱导的tRK1的剧烈构象重排进行，烯醇化酶2将tRK1携带至线粒体前赖氨酸-tRNA合成酶（preMSK）。后者可能穿过线粒体膜到达线粒体基质，在那里导入的tRK1可被线粒体翻译装置利用。这项工作重点研究了tRK1与人类烯醇化酶形成的复合物的特性及其在tRK1与人类前赖氨酸-tRNA合成酶（preKARS2）相互作用中的作用。
