Effect of intronic sequences on splicing regulation of Spinal Muscular Atrophy gene

Spinal muscular atrophy (SMA), which affects young infants, is an autosomal recessive disease caused by a mutation in the Survival Motor Neuron 1 (SMN1) gene. There is a second gene called Survival Motor Neuron 2 (SMN2) that is a nearly identical copy of SMN1. The presence of SMN2 is not enough to compensate for the loss of SMN1 because exon 7 of SMN2 is predominantly skipped during pre-mRNA splicing. In this study, a screen was conducted to search for novel cis-acting regulatory elements that modify and control the splicing of SMN2 pre-mRNA. It was hypothesized that if there remain critical unknown cis-elements that regulate SMN2 pre-mRNA slicing, then by finding these elements the scientific community can gain a better understanding of this splicing. The screen was performed using an engineered reporter system to generate 10 base pair (bp) deletions within SMN2 intron 7. The splicing products of each mutated reporter system were analyzed using gel electrophoresis. From these products a novel branch point shift within intron 7 was identified. Based on these findings, subsequent research is needed to further characterize this branch point shift in hopes of fully understanding the mechanism behind SMN2 pre-mRNA splicing.