Ortiz Raúl, Georgieva Maya V, Gutiérrez Sara, Pedraza Neus, Fernández-Moya Sandra M, Gallego Carme
Molecular Biology Institute of Barcelona (IBMB-CSIC), 08028 Barcelona, Catalonia, Spain.
Institut de Recerca Biomèdica de Lleida (IRBLleida), Departament de Ciències Mèdiques Bàsiques, Universitat de Lleida, 25198 Lleida, Catalonia, Spain.
Cell Rep. 2017 Jul 5;20(1):13-20. doi: 10.1016/j.celrep.2017.06.026.
Regulation of mRNA localization is a conserved cellular process observed in many types of cells and organisms. Asymmetrical mRNA distribution plays a particularly important role in the nervous system, where local translation of localized mRNA represents a key mechanism in synaptic plasticity. CaMKIIα is a very abundant mRNA detected in neurites, consistent with its crucial role at glutamatergic synapses. Here, we report the presence of CaMKIIα mRNA isoforms that contain intron i16 in dendrites, RNA granules, and synaptoneurosomes from primary neurons and brain. This subpopulation of unspliced mRNA preferentially localizes to distal dendrites in a synaptic-activity-dependent manner. Staufen2, a well-established marker of RNA transport in dendrites, interacts with intron i16 sequences and enhances its distal dendritic localization, pointing to the existence of intron-mediated mechanisms in the molecular pathways that modulate dendritic transport and localization of synaptic mRNAs.
mRNA定位的调控是在多种类型的细胞和生物体中观察到的一种保守的细胞过程。不对称的mRNA分布在神经系统中起着特别重要的作用，其中局部mRNA的局部翻译是突触可塑性的关键机制。CaMKIIα是在神经突中检测到的一种非常丰富的mRNA，与其在谷氨酸能突触中的关键作用一致。在这里，我们报告了在原代神经元和大脑的树突、RNA颗粒和突触神经小体中存在含有内含子i16的CaMKIIα mRNA亚型。这种未剪接mRNA的亚群以突触活动依赖的方式优先定位于远端树突。Staufen2是树突中RNA运输的一个公认标记物，它与内含子i16序列相互作用并增强其远端树突定位，表明在调节突触mRNA的树突运输和定位的分子途径中存在内含子介导的机制。
