Heidelberg University, Biochemistry Center, Cluster of Excellence CellNetworks, 69120 Heidelberg, Germany.
Eberhard-Karls-University Tübingen, Interfaculty Institute of Biochemistry, Hoppe-Seyler-Straße 4, 72076 Tübingen, Germany.
Trends Cell Biol. 2019 Feb;29(2):178-188. doi: 10.1016/j.tcb.2018.10.005. Epub 2018 Nov 16.
Proteins are positioned and act at defined subcellular locations. This is particularly important in eukaryotic cells that deliver proteins to membrane-bound organelles such as the endoplasmic reticulum (ER), mitochondria, or endosomes. It is axiomatic that organelle targeting depends mainly on polypeptide signals. However, recent results demonstrate that targeting elements within the encoding transcripts are essential for efficient protein localisation. Key readers of these elements are membrane-associated RNA-binding proteins (memRBPs) that orchestrate organelle-coupled translation. The translation products then either cross the membrane for organelle entry or hitchhike on organelle surfaces for complex assembly and co-transport. Understanding the interaction of protein- and RNA-based targeting signals is essential to decipher the molecular basis for mutant phenotypes in disease.
蛋白质在特定的亚细胞位置定位和发挥作用。在真核细胞中,这一点尤为重要,因为真核细胞需要将蛋白质输送到内质网 (ER)、线粒体或内体等膜结合细胞器中。不言而喻,细胞器的靶向主要依赖于多肽信号。然而,最近的研究结果表明,编码转录本中的靶向元件对于蛋白质的有效定位是必不可少的。这些元件的关键解读者是膜相关 RNA 结合蛋白(memRBPs),它们协调细胞器相关的翻译。然后,翻译产物要么穿过膜进入细胞器,要么搭便车在细胞器表面进行复杂的组装和共运输。理解蛋白质和基于 RNA 的靶向信号的相互作用对于破译疾病中突变表型的分子基础至关重要。