Functional analysis of Survival Motor Neuron protein in Neuronal cells.

运动神经元存活蛋白（SurvivalMotorNeuron，SMN）参与snRNP的组装，是剪接的重要组成部分。 由于SMN 1基因的同源性缺失而导致的SMN缺乏导致遗传性神经退行性疾病，脊髓性肌萎缩症（SMA）。 先前我们发现通过RNAi处理特异性抑制hnRNP A2诱导SMA患者成纤维细胞中SMN产生的减少。 我们已经分析了这种调节的分子细节。 我们提供的证据表明hnRNPA 2特异性结合SMN mRNA的3-UTR的A2结合序列，并增加mRNA和多聚核糖体的相互作用，以提高翻译效率。我们的数据表明，hnRNP A2是必要的SMN 1/2 mRNA的有效翻译，这A2结合位点的功能作为一个翻译增强子。 我们的研究结果不仅明确了hnRNP A2特异性调控SMN翻译的新机制，而且为SMA治疗药物的开发提供了新的思路。

Survival Motor Neuron (SMN) protein is involved in snRNPs assembly, essential components in splicing. A lack of SMN due to homologous loss of SMN1 gene results hereditary neurodegenerative disease, Spinal Muscular Atrophy (SMA). Previously we found that the specific suppression of hnRNP A2 by RNAi treatment induced a reduction of SMN production in SMA patient fibroblast cell. We have analyzed the molecular detail of this regulation. We provided evidences that hnRNP A2 specifically binds A2 binding sequence at 3-UTR of SMN mRNA, and increases the interaction of mRNAs and polyribosome to enhance translation efficiency. Our data suggests that hnRNP A2 is essential for the effective translation of SMN1/2 mRNA, and that this A2 binding site functions as a translation enhancer. Our findings not only define the new regulatory mechanism to control SMN translation by hnRNP A2 specifically, but also implicate the new therapeutic drug development for treatment of SMA.