Cho Sunghee, Moon Heegyum, Loh Tiing Jen, Oh Hyun Kyung, Kim Hey-Ran, Shin Myung-Geun, Liao D Joshua, Zhou Jianhua, Zheng Xuexiu, Shen Haihong
School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 500-712, Republic of Korea.
Department of Laboratory Medicine, Chonnam National University Medical School and Chonnam National University Hwasun Hospital, Hwasun 519-763, Republic of Korea.
ScientificWorldJournal. 2014 Jan 27;2014:617842. doi: 10.1155/2014/617842. eCollection 2014.
Spinal muscular atrophy (SMA) is a human genetic disease which occurs because of the deletion or mutation of SMN1 gene. SMN1 gene encodes the SMN protein which plays a key role in spliceosome assembly. Although human patients contain SMN2, a duplicate of SMN1, splicing of SMN2 produces predominantly exon 7 skipped isoform. In order to understand the functions of splice site sequences on exon 7 and 8, we analyzed the effects of conserved splice site sequences on exon 7 skipping of SMN2 and SMN1 pre-mRNA. We show here that conserved 5' splice site sequence of exon 7 promoted splicing of nearby exons and subsequently reduced splicing of distant exons. However, to our surprise, conserved 3' splice site sequence of exon 7 and 8 did not promote splicing of nearby exons. By contrast, the mutation inhibited splicing of nearby exons and subsequently promoted splicing of distant exons. Our study shows that 3' splice sites of exon 7 and 8 contain enhancer for their splice site selection, in addition to providing cleavage sites.
脊髓性肌萎缩症（SMA）是一种人类遗传疾病，它是由于SMN1基因的缺失或突变而发生的。SMN1基因编码SMN蛋白，该蛋白在剪接体组装中起关键作用。尽管人类患者含有SMN2（SMN1的一个拷贝），但SMN2的剪接主要产生外显子7缺失的异构体。为了了解外显子7和8上剪接位点序列的功能，我们分析了保守剪接位点序列对SMN2和SMN1前体mRNA外显子7跳跃的影响。我们在此表明，外显子7保守的5'剪接位点序列促进了附近外显子的剪接，随后减少了远处外显子的剪接。然而，令我们惊讶的是，外显子7和8保守的3'剪接位点序列并未促进附近外显子的剪接。相反，该突变抑制了附近外显子的剪接，随后促进了远处外显子的剪接。我们的研究表明，外显子7和8的3'剪接位点除了提供切割位点外，还包含其剪接位点选择的增强子。
