Predominant expression of exon 7 skipped SMN mRNAs in lung based on analysis of transcriptome sequencing datasets

Abstract

Spinal muscular atrophy (SMA) is caused by deletion of SMN1, one of the two SMN (Survival of Motor Neuron) genes. SMN2 is still present in SMA patients but its exon 7 is alternatively spliced. In this study, we took advantage of recent deposit of deep-sequencing datasets from a number of human tissues and examined the expression and splicing of SMN mRNA. We showed that SMN is slightly more abundantly expressed in the lungs and prostate. More interestingly, we found that the percentage of SMN Delta 7 in lung and adipose tissue is significantly higher than in other tissues such as the testes, where almost no SMND7 is expressed. Since SMN1 produces more than 95 % of full-length SMN RNA, it is likely that SMN2 has a higher skipping rate of exon 7 in adipose and lung tissue, leading to a higher ratio of SMND Delta 7/SMN in these tissues. Given that many SMA patients die from respiratory failure, we speculate that higher skipping of exon 7 in the lungs may play a role in the progression of SMA.