A Drosophila model of spinal muscular atrophy uncouples snRNP biogenesis functions of survival motor neuron from locomotion and viability defects.
A Drosophila model of spinal muscular atrophy uncouples snRNP biogenesis functions of survival motor neuron from locomotion and viability defects.
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DOI：
10.1016/j.celrep.2012.05.014
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发表时间：
2012-06-28
期刊：
影响因子：
8.8
通讯作者：
Matera AG
中科院分区：
文献类型：
--
作者：
Praveen K;Wen Y;Matera AG
脊髓性肌萎缩（SMA）蛋白，运动神经元存活（SMN），在小核核糖核蛋白（snRNP）的生物发生中起作用。SMN也与组织特异性功能有关，但仍不清楚哪些功能对SMA的病因学很重要。Smn无效突变体是幼虫致死的，并显示出显着的运动缺陷，以及减少次要类spliceosomal snRNAs。尽管这些减少，我们发现没有明显的缺陷，剪接的mRNA含有次要类内含子。低水平的野生型或SMA患者衍生形式的SMN的转基因表达挽救了幼虫的致死率和运动缺陷，然而，snRNA水平没有恢复。因此，SNRNP生物合成功能的SMN是不是一个主要的贡献者的表型Smn无效突变体。这些发现对SMA病因学具有重要意义，因为它们表明SMN在snRNP生物发生中的作用可以与生物体活力和运动缺陷分离。
The Spinal Muscular Atrophy (SMA) protein, survival motor neuron (SMN), functions in the biogenesis of small nuclear ribonucleoproteins (snRNPs). SMN has also been implicated in tissue-specific functions, however, it remains unclear which of these is important for the etiology of SMA. Smn null mutants are larval lethals and show significant locomotion defects as well as reductions in minor-class spliceosomal snRNAs. Despite these reductions, we found no appreciable defects in splicing of mRNAs containing minor-class introns. Transgenic expression of low levels of either wild-type or an SMA patient-derived form of SMN rescued the larval lethality and locomotor defects, however, snRNA levels were not restored. Thus, the snRNP biogenesis function of SMN is not a major contributor to the phenotype of Smn null mutants. These findings have major implications for SMA etiology because they show that SMN's role in snRNP biogenesis can be uncoupled from the organismal viability and locomotor defects.
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