Survival motor neuron 2 pre-messenger RNA (SMN2 pre-mRNA)

Survival motor neuron 2 pre-messenger RNA (SMN2 pre-mRNA) is the unspliced RNA transcript produced from the SMN2 gene, a paralog of the SMN1 gene. It is the molecular substrate for splicing events that determine the inclusion or exclusion of exon 7, which is critical for generating functional SMN protein. Due to a single nucleotide difference from SMN1, SMN2 pre-mRNA is prone to exon 7 skipping during alternative splicing, resulting in truncated, unstable SMN protein insufficient for normal motor neuron function. This deficient splicing is the molecular cause of spinal muscular atrophy (SMA). Therapeutic strategies, including small molecules (e.g., risdiplam, branaplam, SMN-C compounds) and antisense oligonucleotides (e.g., nusinersen), target the splicing machinery or directly bind to SMN2 pre-mRNA to enhance exon 7 inclusion. SMN2 pre-mRNA is thus a validated and clinically exploited therapeutic RNA target for treating SMA, notable both for its biological role in RNA processing and its direct capability to be targeted by small-molecule and nucleic acid therapies.

Other names

SMN2 (when context refers to the RNA, though strictly, SMN2 gene is the DNA locus)SMN2 transcriptSurvival motor neuron 2 pre-mRNA

Small molecule binding to specific RNA secondary structures to modulate exon 7 inclusion (e.g., risdiplam, SMN-C2/C3); Stabilization/alteration of RNA-protein complexes promoting exon 7 inclusion/skipping reversal; Antisense oligonucleotide-mediated splicing alteration (e.g., nusinersen, enhances exon 7 inclusion by blocking splicing repressors)