Irimura Sanae, Kitamura Keiko, Kato Nozomu, Saiki Kayoko, Takeuchi Atsuko, Matsuo Masafumi, Nishio Hisahide, Lee Myeong Jin
Department of Genetic Epidemiology, Kobe University Graduate School of Medicine, Kobe, Japan.
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。
