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. 2022 Jun 10;11(6):894. doi: 10.3390/biology11060894

Figure 1.

Figure 1

Genetic overview of spinal muscular atrophy. (A) Human chromosome 5q13 is encompassed by a telomeric SMN1 gene and a centromeric SMN2 gene. (B) Splicing of SMN1 pre-mRNA produces full-length mRNA that is translated into functional SMN protein containing a Tudor domain, a proline-rich region, and a YG-box domain. On the other hand, splicing of SMN2 pre-mRNA translates into a functional SMN protein in ~10% of cases, and splicing of SMN2 pre-mRNA produces SMN2 mRNA without exon 7 (SMN2Δ7), translating a truncated protein easily degraded in ~90% of cases. Lastly, (C) shows exon 7 splicing in SMN1 and SMN2 genes. The exonic splice enhancer (ESE) promotes the translation of full-length SMN1 protein. The C-to-T transition leads to the formation of an exonic splice suppressor (ESS), which binds the heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) and translates an unstable SMNΔ7 protein. Antisense oligonucleotides (i.e., nusinersen) target the intronic splice silencer (ISS-N1), preventing the binding of hnRNP A1 and promoting exon 7 inclusion and subsequent translation of full-length SMN protein.