Ubiquitin protein ligase E3A antisense RNA (UBE3A-ATS) (UBE3A-ATS)

The Ubiquitin protein ligase E3A antisense RNA (UBE3A-ATS) is a long non-coding RNA (lncRNA) that mediates the neuron-specific epigenetic silencing of the paternal UBE3A allele (PubMed: 25339411). In healthy neurons, UBE3A-ATS is expressed from the paternal chromosome and prevents the expression of the paternal UBE3A gene through transcriptional interference, leaving the maternal allele as the sole source of UBE3A protein. Angelman Syndrome is a neurodevelopmental disorder caused by the loss of function of the maternal UBE3A allele, which results in a deficiency of the UBE3A protein in the brain because the paternal copy remains silenced by UBE3A-ATS (NIH: NBK1144). UBE3A-ATS has emerged as a primary therapeutic target; by using antisense oligonucleotides (ASOs) to degrade this transcript, researchers can unsilence the paternal UBE3A gene and restore protein levels (Nature: 10.1038/nature13975). Several investigational therapies, including GTX-102 and Rugonersen, are currently in clinical development to evaluate this mechanism's ability to improve motor, speech, and cognitive symptoms in patients (ClinicalTrials.gov: NCT04259281).

Other names

UBE3A-ASUBE3A antisense transcriptSNHG14UBE3A-AS1LNC-UBE3A-ATS

Antisense oligonucleotide-mediated degradation of the UBE3A-ATS transcript to reactivate the silenced paternal UBE3A allele.