Functional analysis of Survival Motor Neuron protein in Neuronal cells.

存活运动神经元(SMN)蛋白参与了SNRNPs的组装，这是剪接过程中的重要组成部分。由于SMN1基因同源缺失导致的SMN缺失导致遗传性神经退行性疾病，即脊髓性肌萎缩(SMA)。以前我们发现，RNAi治疗对hnRNP A2的特异性抑制导致SMA患者成纤维细胞SMN合成减少。我们已经分析了这一规定的分子细节。我们提供的证据表明，hnRNP A2特异性地结合SMN mRNA 3-UTR处的A2结合序列，并增加mRNAs与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对于SMN1/2 mRNA的有效翻译是必不可少的，并且这个A2结合位点起到翻译增强剂的作用。我们的发现不仅明确了通过hnRNP A2特异性地控制SMN翻译的新的调控机制，而且也为治疗SMA的新的治疗药物的开发提供了可能。

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.