Caenorhabditis elegans in the study of SMN-interacting proteins:: a role for SMI-1, an orthologue of human Gemin2 and the identification of novel components of the SMN complex

Caenorhabditis elegans in the study of SMN-interacting proteins:: a role for SMI-1, an orthologue of human Gemin2 and the identification of novel components of the SMN complex
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DOI:
10.1007/s10158-006-0027-x
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发表时间:
2006-12-01
影响因子:
--
通讯作者:
Sattelle, David B.
Sattelle, David B.
中科院分区:
生物4区
文献类型:
--
作者:
Burt, Emma C.;Towers, Paula R.;Sattelle, David B.

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脊髓性肌萎缩症是一种常见的神经肌肉疾病,由运动神经元存活基因(SMN)突变引起。在哺乳动物中,SMN与Gemin 2紧密相关。为了进一步了解SMN和Gemin 2的功能,我们克隆并测序了smi-1(运动神经元相互作用蛋白1的生存),这是一种与人类Gemin 2基因同源的线虫同源物。我们发现,SMI-1的表达模式和RNA干扰表型显示出相当大的重叠与以前报道的SMN-1。最后,我们证明了SMN-1和SMI-1蛋白直接相互作用。已经证明了利用线虫遗传模型研究编码SMN相互作用蛋白的基因,我们已经进行了酵母双杂交筛选的线虫cDNA文库,以确定新的蛋白质与SMN-1相互作用。我们展示了SMN-1与9种新蛋白质的直接相互作用,其中几种可能参与RNA代谢。
Spinal muscular atrophy is a common neuromuscular disorder caused by mutations in the survival motor neuron (SMN) gene. In mammals, SMN is tightly associated with Gemin2. To gain further insight into the functions of SMN and Gemin2, we have cloned and sequenced smi-1 (Survival of Motor neuron-Interacting protein 1), a C elegans homologue of the human Gemin2 gene. We show that the SMI-1 expression pattern and RNA interference phenotype show considerable overlap with that previously reported for SMN-1. Finally, we demonstrate that the SMN-1 and SMI-1 proteins directly interact. Having demonstrated the utility of the C elegans genetic model for investigating genes encoding SMN-interacting proteins, we have undertaken a yeast two-hybrid screen of a C elegans cDNA library to identify novel proteins that interact with SMN-1. We show the direct interaction of SMN-1 with nine novel proteins, several of which may be involved in RNA metabolism.