RNA. 2013 Dec;19(12):1755-66. doi: 10.1261/rna.040204.113. Epub 2013 Oct 23.
Spinal muscular atrophy is a neuromuscular disease resulting from mutations in the SMN1 gene, which encodes the survival motor neuron (SMN) protein. SMN is part of a large complex that is essential for the biogenesis of spliceosomal small nuclear RNPs. SMN also colocalizes with mRNAs in granules that are actively transported in neuronal processes, supporting the hypothesis that SMN is involved in axonal trafficking of mRNPs. Here, we have performed a genome-wide analysis of RNAs present in complexes containing the SMN protein and identified more than 200 mRNAs associated with SMN in differentiated NSC-34 motor neuron-like cells. Remarkably, ~30% are described to localize in axons of different neuron types. In situ hybridization and immuno-fluorescence experiments performed on several candidates indicate that these mRNAs colocalize with the SMN protein in neurites and axons of differentiated NSC-34 cells. Moreover, they localize in cell processes in an SMN-dependent manner. Thus, low SMN levels might result in localization deficiencies of mRNAs required for axonogenesis.
脊髓性肌萎缩症是一种由 SMN1 基因突变引起的神经肌肉疾病，该基因编码运动神经元存活蛋白（SMN）。SMN 是一个大型复合物的一部分，该复合物对于剪接体小核 RNP 的生物发生至关重要。SMN 还与在神经元过程中主动运输的颗粒中的 mRNA 共定位，支持 SMN 参与 mRNP 的轴突运输的假说。在这里，我们对包含 SMN 蛋白的复合物中的 RNA 进行了全基因组分析，并在分化的 NSC-34 运动神经元样细胞中鉴定出 200 多个与 SMN 相关的 mRNA。值得注意的是，约 30%的 mRNAs 被描述为定位于不同神经元类型的轴突中。对几个候选物进行的原位杂交和免疫荧光实验表明，这些 mRNA 与分化的 NSC-34 细胞中的 SMN 蛋白在神经突和轴突中共定位。此外，它们以 SMN 依赖性的方式定位于细胞过程中。因此，SMN 水平低可能导致轴突发生所需的 mRNA 定位缺陷。
