HnRNP C1/C2 may regulate exon 7 splicing in the spinal muscular atrophy gene SMN1.

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.