Department of Chemistry and Biochemistry, University of California at Los Angeles, Los Angeles, CA 90095, USA.
Cell. 2010 Aug 6;142(3):456-67. doi: 10.1016/j.cell.2010.06.035.
RNA import into mammalian mitochondria is considered essential for replication, transcription, and translation of the mitochondrial genome but the pathway(s) and factors that control this import are poorly understood. Previously, we localized polynucleotide phosphorylase (PNPASE), a 3' --> 5' exoribonuclease and poly-A polymerase, in the mitochondrial intermembrane space, a location lacking resident RNAs. Here, we show a new role for PNPASE in regulating the import of nuclear-encoded RNAs into the mitochondrial matrix. PNPASE reduction impaired mitochondrial RNA processing and polycistronic transcripts accumulated. Augmented import of RNase P, 5S rRNA, and MRP RNAs depended on PNPASE expression and PNPASE-imported RNA interactions were identified. PNPASE RNA processing and import activities were separable and a mitochondrial RNA targeting signal was isolated that enabled RNA import in a PNPASE-dependent manner. Combined, these data strongly support an unanticipated role for PNPASE in mediating the translocation of RNAs into mitochondria.
哺乳动物线粒体中的 RNA 导入被认为对线粒体基因组的复制、转录和翻译至关重要,但控制这种导入的途径和因素还知之甚少。此前,我们将多核苷酸磷酸化酶 (PNPASE) 定位在缺少常驻 RNA 的线粒体膜间隙中,PNPASE 是一种 3' --> 5' 外切核糖核酸酶和聚 A 聚合酶。在这里,我们展示了 PNPASE 在调节核编码 RNA 导入线粒体基质中的新作用。PNPASE 的减少会损害线粒体 RNA 的加工,导致多顺反子转录本的积累。依赖于 PNPASE 表达和 PNPASE 导入 RNA 相互作用,增加了 RNase P、5S rRNA 和 MRP RNA 的导入。PNPASE 的 RNA 加工和导入活性是可分离的,并且分离出了一个线粒体 RNA 靶向信号,该信号能够以 PNPASE 依赖的方式进行 RNA 导入。综上所述,这些数据强烈支持 PNPASE 在介导 RNA 转运进入线粒体中的意外作用。