Sendtner M
Institute for Clinical Neurobiology, University of Wuerzburg, Wuerzburg, Germany.
Curr Opin Neurol. 2001 Oct;14(5):629-34. doi: 10.1097/00019052-200110000-00012.
Spinal muscular atrophy is an autosomal-recessive disorder that is caused by homozygous mutations or deletion of the telomeric copy of the survival of motor neurone (SMN) gene on human chromosome 5q13. The SMN gene is present as an inverted repeat in this chromosomal region, and both SMN genes are expressed. They differ by the preferential expression of a full-length transcript from the telomeric copy and a truncated SMN protein from the centromeric SMN gene, which lacks the carboxyl-terminal portions of the protein encoded by exon 7. The SMN protein is part of multiprotein complexes in the cytoplasm and the nucleus that are involved in spliceosomal small-nuclear RNP assembly. This function depends on interaction with spliceosomal Sm core proteins. Recent data have also shown that the SMN protein interacts with RNA polymerase II, thus implying additional functions in messenger RNA transcription, possibly by assembly of RNA polymerase II transcription complexes. Thus, the SMN protein is involved in critical steps of messenger RNA transcription and processing, and current research efforts are directed at identifying the specificity of these defects for the pathophysiological changes in motor neurones that occur in spinal muscular atrophy.
脊髓性肌萎缩症是一种常染色体隐性疾病，由人类5号染色体q13区域运动神经元存活（SMN）基因端粒拷贝的纯合突变或缺失引起。SMN基因在该染色体区域以反向重复形式存在，两个SMN基因均表达。它们的区别在于端粒拷贝的全长转录本优先表达，而着丝粒SMN基因的SMN蛋白截短，缺少外显子7编码的蛋白质的羧基末端部分。SMN蛋白是细胞质和细胞核中多蛋白复合物的一部分，参与剪接体小核核糖核蛋白组装。该功能依赖于与剪接体Sm核心蛋白的相互作用。最近的数据还表明，SMN蛋白与RNA聚合酶II相互作用，因此意味着在信使RNA转录中可能通过RNA聚合酶II转录复合物的组装发挥其他功能。因此，SMN蛋白参与信使RNA转录和加工的关键步骤，目前的研究工作旨在确定这些缺陷对脊髓性肌萎缩症中运动神经元病理生理变化的特异性。
