Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology (BIST), Doctor Aiguader 88, Barcelona 08003, Spain.
ICFO, Castelldelfels, Spain.
Sci Adv. 2020 Mar 13;6(11):eaaz1588. doi: 10.1126/sciadv.aaz1588. eCollection 2020 Mar.
Through the asymmetric distribution of messenger RNAs (mRNAs), cells spatially regulate gene expression to create cytoplasmic domains with specialized functions. In neurons, mRNA localization is required for essential processes such as cell polarization, migration, and synaptic plasticity underlying long-term memory formation. The essential components driving cytoplasmic mRNA transport in neurons and mammalian cells are not known. We report the first reconstitution of a mammalian mRNA transport system revealing that the tumor suppressor adenomatous polyposis coli (APC) forms stable complexes with the axonally localized β-actin and β2B-tubulin mRNAs, which are linked to a kinesin-2 via the cargo adaptor KAP3. APC activates kinesin-2, and both proteins are sufficient to drive specific transport of defined mRNA packages. Guanine-rich sequences located in 3'UTRs of axonal mRNAs increase transport efficiency and balance the access of different mRNAs to the transport system. Our findings reveal a minimal set of proteins sufficient to transport mammalian mRNAs.
通过信使 RNA（mRNA）的不对称分布，细胞在空间上调节基因表达，从而产生具有特殊功能的细胞质域。在神经元中，mRNA 的定位对于细胞极化、迁移和突触可塑性等基本过程是必需的，这些过程是长时记忆形成的基础。驱动神经元和哺乳动物细胞中细胞质 mRNA 运输的基本成分尚不清楚。我们首次重建了哺乳动物 mRNA 运输系统，结果表明，肿瘤抑制因子腺瘤性结肠息肉病基因（APC）与轴突定位的β-肌动蛋白和β2B-微管蛋白形成稳定的复合物，该复合物通过货物衔接蛋白 KAP3 与驱动蛋白-2 相连。APC 激活驱动蛋白-2，这两种蛋白足以驱动特定的 mRNA 包的特异性运输。位于轴突 mRNA 3'UTR 中的鸟嘌呤富集序列提高了运输效率，并平衡了不同 mRNA 对运输系统的访问。我们的研究结果揭示了一组足以运输哺乳动物 mRNA 的最小蛋白。
