Survival of motor neuron 2 pre-mRNA exonic splicing enhancer 2 (SMN2 ESE2)

The Survival of motor neuron 2 (SMN2) pre-mRNA exonic splicing enhancer 2 (ESE2) is a regulatory RNA sequence located within exon 7 of the SMN2 gene [1]. In Spinal Muscular Atrophy (SMA), the loss of the SMN1 gene makes survival dependent on the nearly identical SMN2 gene; however, a C-to-T transition in SMN2 exon 7 disrupts splicing regulatory elements, causing the exclusion of exon 7 in approximately 90% of transcripts and resulting in a truncated, unstable protein [2]. ESE2 is a critical target for small molecule splicing modifiers like Risdiplam, which bind specifically to both ESE2 and the 5' splice site of exon 7 to stabilize the U1 snRNP-pre-mRNA complex [3]. This binding promotes the inclusion of exon 7 during pre-mRNA processing, leading to increased production of functional, full-length SMN protein [4]. By restoring SMN protein levels, therapeutic targeting of ESE2 addresses the underlying cause of motor neuron degeneration and muscle atrophy in SMA patients [5].

Other names

SMN2 exon 7 ESE2SMN2 exonic splicing enhancer 2SMN2 pre-mRNA ESE2Survival of motor neuron 2 exon 7 exonic splicing enhancer 2

Small molecule-induced stabilization of the U1 snRNP at the 5' splice site through cooperative binding with the ESE2 sequence, promoting exon 7 inclusion.