Survival motor neuron antisense RNA 1 (SMN-AS1)

Survival motor neuron antisense RNA 1 (SMN-AS1) is a neuronally-enriched, long non-coding RNA transcribed antisense to the SMN gene locus, mainly from a region within intron 1 of both SMN1 and SMN2 genes[1][3]. SMN-AS1 plays a regulatory role by recruiting the Polycomb repressive complex 2 (PRC2) to the SMN promoter, thereby repressing SMN gene transcription, which leads to lower levels of SMN protein—a critical factor for motor neuron survival. Knockdown of SMN-AS1 using antisense oligonucleotides has been shown to increase SMN protein expression both in cell and animal models, improving outcomes in spinal muscular atrophy (SMA), indicating its potential as a novel therapeutic target[1][3]. There is evidence that combinatorial approaches targeting both SMN-AS1 (to enhance transcription) and SMN2 splicing (to correct mRNA processing) have additive beneficial effects in SMA models, highlighting the promise of lncRNA modulation as a therapeutic strategy for neurogenetic diseases[1].

Other names

SMN1-AS1SMN-AS1survival motor neuron-antisense 1

ASOs against SMN-AS1: Knockdown of SMN-AS1 reduces its function, dissociates PRC2 from the SMN promoter, and increases transcription of SMN genes resulting in higher SMN protein levels[1][3].