异质性核糖核蛋白C1/C2可能调控脊髓性肌萎缩症基因SMN1中外显子7的剪接。
HnRNP C1/C2 may regulate exon 7 splicing in the spinal muscular atrophy gene SMN1.
作者信息
Irimura Sanae, Kitamura Keiko, Kato Nozomu, Saiki Kayoko, Takeuchi Atsuko, Matsuo Masafumi, Nishio Hisahide, Lee Myeong Jin
机构信息
Department of Genetic Epidemiology, Kobe University Graduate School of Medicine, Kobe, Japan.
出版信息
Kobe J Med Sci. 2009 Mar 10;54(5):E227-36.
Spinal muscular atrophy (SMA) is caused by loss of SMN1. A nearly identical gene, SMN2, fails to compensate for the loss of SMN1 because SMN2 produces mainly an exon 7-skipped product. The +6C in SMN1 exon 7 proceeds to include exon 7 into mRNA, while the +6U in SMN2 causes skipping of exon 7. Here, approximately 45kD proteins bound to the SMN exon 7 RNA probe was found, and identified as hnRNP C1/C2. In gel-shift assay, hnRNP C1/C2 had a greater affinity for the RNA probe with +6C than for the RNA probe with +6U. In vitro splicing assay showed that anti-hnRNP C1/C2 antibody hampered splicing of SMN1 exon 7, but did not affect splicing of SMN2 exon 7. In conclusion, we showed the possibility that hnRNP C1/C2 enhanced SMN1 exon 7 splicing specifically.
脊髓性肌萎缩症（SMA）是由SMN1缺失引起的。一个几乎相同的基因SMN2无法补偿SMN1的缺失，因为SMN2主要产生一种缺失外显子7的产物。SMN1外显子7中的+6C会使外显子7包含在mRNA中，而SMN2中的+6U则导致外显子7的缺失。在此，发现了与SMN外显子7 RNA探针结合的约45kD蛋白质，并鉴定为hnRNP C1/C2。在凝胶迁移试验中，hnRNP C1/C2对带有+6C的RNA探针的亲和力比对带有+6U的RNA探针的亲和力更高。体外剪接试验表明，抗hnRNP C1/C2抗体阻碍了SMN1外显子7的剪接，但不影响SMN2外显子7的剪接。总之，我们证明了hnRNP C1/C2特异性增强SMN1外显子7剪接的可能性。
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