Specific interaction of Smn, the spinal muscular atrophy determining gene product, with hnRNP-R and gry-rbp/hnRNP-Q:: a role for Smn in RNA processing in motor axons?
Specific interaction of Smn, the spinal muscular atrophy determining gene product, with hnRNP-R and gry-rbp/hnRNP-Q:: a role for Smn in RNA processing in motor axons?
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DOI：
10.1093/hmg/11.1.93
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发表时间：
2002-01-01
影响因子：
3.5
通讯作者：
Sendtner, M
中科院分区：
文献类型：
--
作者：
Rossoll, W;Kröning, AK;Sendtner, M
脊髓性肌萎缩症（SMA）是儿童和年轻人中最常见的遗传性运动神经元疾病，是由端粒运动神经元生存（SMN 1）基因突变引起的。与小鼠相反，人类基因组含有第二个SMN基因（SMN 2），其编码在C末端选择性剪接的基因产物，但也产生低水平的全长SMN蛋白。普遍表达的SMN蛋白水平降低导致特定运动神经元变性而不影响其他细胞类型的原因仍不清楚。利用酵母双杂交技术，我们确定hnRNP-R和高度相关的gry-rbp/hnRNP-Q作为新的SMN相互作用伙伴。这些蛋白质先前已经在RNA加工的背景下被鉴定，特别是mRNA编辑、运输和剪接。hnRNP-R和gry-rbp/hnRNP-Q与野生型Smn相互作用，但不与SMA中鉴定的截短型或突变型Smn相互作用。这两种蛋白质在小鼠脊髓中广泛表达并发育调节，表达峰值在E19。hnRNP-R通过其RNA识别基序结构域结合RNA。有趣的是，hnRNP-R主要位于运动神经元的轴突中，并与Smn共同定位在该细胞区室中。因此，这一发现可能为理解SMA中运动神经元特异性Smn功能提供了一把钥匙。
Spinal muscular atrophy (SMA), the most common hereditary motor neuron disease in children and young adults is caused by mutations in the telomeric survival motor neuron (SMN1) gene. The human genome, in contrast to mouse, contains a second SMN gene (SMN2) which codes for a gene product which is alternatively spliced at the C-terminus, but also gives rise to low levels of full-length SMN protein. The reason why reduced levels of the ubiquitously expressed SMN protein lead to specific motor neuron degeneration without affecting other cell types is still not understood. Using yeast two-hybrid techniques, we identified hnRNP-R and the highly related gry-rbp/hnRNP-Q as novel SMN interaction partners. These proteins have previously been identified in the context of RNA processing, in particular mRNA editing, transport and splicing. hnRNP-R and gry-rbp/hnRNP-Q interact with wild-type Smn but not with truncated or mutant Smn forms identified in SMA. Both proteins are widely expressed and developmentally regulated with expression peaking at E19 in mouse spinal cord. hnRNP-R binds RNA through its RNA recognition motif domains. Interestingly, hnRNP-R is predominantly located in axons of motor neurons and co-localizes with Smn in this cellular compartment. Thus, this finding could provide a key to understand a motor neuron-specific Smn function in SMA.