An intronic splicing enhancer element in survival motor neuron (SMN) Pre-mRNA

被引:61
作者
Miyaso, H [1 ]
Okumura, M [1 ]
Kondo, S [1 ]
Higashide, S [1 ]
Miyajima, H [1 ]
Imaizumi, K [1 ]
机构
[1] Nara Inst Sci & Technol, Div Struct Cellular Biol, Nara 6300101, Japan
关键词
D O I
10.1074/jbc.M209271200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Spinal muscular atrophy is caused by the homozygous loss of survival motor neuron 1 (SMN1). SMN2, a nearly identical copy gene, differs from SMN1 only by a single nonpolymorphic C to T transition in exon 7, which leads to alteration of exon 7 splicing; SMN2 leads to exon 7 skipping and expression of a nonfunctional gene product and fails to compensate for the loss of SMN1. The exclusion of SMN exon 7 is critical for the onset of this disease. Regulation of SMN exon 7 splicing was determined by analyzing the roles of the cis-acting element in intron 7 (element 2), which we previously identified as a splicing enhancer element of SMN exon 7 containing the C to T transition. The minimum sequence essential for activation of the splicing was determined to be 24 nucleotides, and RNA structural analyses showed a stem-loop structure. Deletion of this element or disruption of the stem-loop structure resulted in a decrease in exon 7 inclusion. A gel shift assay using element 2 revealed formation of RNA-protein complexes, suggesting that the binding of the trans-acting proteins to element 2 plays a crucial role in the splicing of SMN exon 7 containing the C to T transition.
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收藏
页码:15825 / 15831
页数:7
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