Center for Cell Biology and Cancer Research, Albany Medical College, Albany, NY 12208, USA.
J Cell Sci. 2011 Feb 15;124(Pt 4):589-99. doi: 10.1242/jcs.072421. Epub 2011 Jan 25.
Signal-peptide-mediated ER localization of mRNAs encoding for membrane and secreted proteins, and RNA-zipcode-mediated intracellular targeting of mRNAs encoding for cytosolic proteins are two well-known mechanisms for mRNA localization. Here, we report a previously unidentified mechanism by which mRNA encoding for Dia1, a cytosolic protein without the signal peptide, is localized to the perinuclear ER in an RNA-zipcode-independent manner in fibroblasts. Dia1 mRNA localization is also independent of the actin and microtubule cytoskeleton but requires translation and the association of Dia1 nascent peptide with the ribosome-mRNA complex. Sequence mapping suggests that interactions of the GTPase binding domain of Dia1 peptide with active Rho are important for Dia1 mRNA localization. This mechanism can override the β-actin RNA zipcode and redirect β-actin mRNA to the perinuclear region, providing a new way to manipulate intracellular mRNA localization.
信号肽介导的膜蛋白和分泌蛋白编码 mRNA 的内质网定位，以及 RNA 拉链码介导的胞质蛋白编码 mRNA 的细胞内靶向，是两种已知的 mRNA 定位机制。在这里，我们报道了一种以前未被识别的机制，即在成纤维细胞中，无信号肽的胞质蛋白 Dia1 的编码 mRNA 以 RNA 拉链码独立的方式被定位到核周内质网。Dia1 mRNA 的定位也不依赖于肌动蛋白和微管细胞骨架，但需要翻译和 Dia1 新生肽与核糖体-mRNA 复合物的结合。序列图谱表明，Dia1 肽的 GTP 结合域与活性 Rho 的相互作用对于 Dia1 mRNA 的定位很重要。这种机制可以覆盖 β-actin RNA 拉链码，并将 β-actin mRNA 重新引导到核周区域，为操纵细胞内 mRNA 定位提供了一种新方法。
