The mammalian mitochondrial proteome comprises over 1000 proteins, with the majority translated from nuclear-encoded messenger RNAs (mRNAs). Mounting evidence suggests many of these mRNAs are localized to the outer mitochondrial membrane (OMM) in a pre- or cotranslational state. Upon reaching the mitochondrial surface, these mRNAs are locally translated to produce proteins that are cotranslationally imported into mitochondria. Here, we summarize various mechanisms cells use to localize RNAs, including transfer RNAs (tRNAs), to the OMM and recent technological advancements in the field to study these processes. While most early studies in the field were carried out in yeast, recent studies reveal RNA localization to the OMM and their regulation in higher organisms. Various factors regulate this localization process, including RNA sequence elements, RNA-binding proteins (RBPs), cytoskeletal motors, and translation machinery. In this review, we also highlight the role of RNA structures and modifications in mitochondrial RNA localization and discuss how these features can alter the binding properties of RNAs. Finally, in addition to RNAs related to mitochondrial function, RNAs involved in other cellular processes can also localize to the OMM, including those implicated in the innate immune response and piRNA biogenesis. As impairment of messenger RNA (mRNA) localization and regulation compromise mitochondrial function, future studies will undoubtedly expand our understanding of how RNAs localize to the OMM and investigate the consequences of their mislocalization in disorders, particularly neurodegenerative diseases, muscular dystrophies, and cancers.

中文翻译：

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RNA 定位到线粒体——机制和功能


哺乳动物线粒体蛋白质组包含 1000 多种蛋白质，其中大部分由核编码的信使 RNA (mRNA) 翻译而来。越来越多的证据表明，许多这些 mRNA 以翻译前或共翻译状态定位于线粒体外膜 (OMM)。到达线粒体表面后，这些 mRNA 进行局部翻译，产生共翻译导入线粒体的蛋白质。在这里，我们总结了细胞用于将 RNA（包括转移 RNA (tRNA)）定位到 OMM 的各种机制，以及该领域研究这些过程的最新技术进展。虽然该领域的大多数早期研究都是在酵母中进行的，但最近的研究揭示了 RNA 定位到 OMM 及其在高等生物中的调节。多种因素调节这一定位过程，包括 RNA 序列元件、RNA 结合蛋白 (RBP)、细胞骨架马达和翻译机制。在这篇综述中，我们还强调了 RNA 结构和修饰在线粒体 RNA 定位中的作用，并讨论了这些特征如何改变 RNA 的结合特性。最后，除了与线粒体功能相关的 RNA 之外，参与其他细胞过程的 RNA 也可以定位于 OMM，包括那些与先天免疫反应和 piRNA 生物发生有关的 RNA。由于信使 RNA (mRNA) 定位和调节的受损会损害线粒体功能，未来的研究无疑将扩大我们对 RNA 如何定位到 OMM 的理解，并研究它们错误定位在疾病中的后果，特别是神经退行性疾病、肌肉营养不良和癌症。