UBE3A antisense transcript long non-coding RNA (UBE3A-ATS)

UBE3A antisense transcript (UBE3A-ATS) is a very long non-coding RNA (lncRNA) that plays a pivotal role in the tissue-specific genomic imprinting of the UBE3A gene within the central nervous system (Meng et al., 2015, Nature). In healthy neurons, UBE3A-ATS is expressed exclusively from the paternal chromosome and extends across the UBE3A locus in the antisense direction, which effectively silences the paternal UBE3A allele through transcriptional interference (Runte et al., 2001, Human Molecular Genetics). Angelman syndrome is a severe neurodevelopmental disorder caused by the loss of function of the maternal UBE3A allele; because the paternal copy is naturally silenced by UBE3A-ATS, the brain lacks the essential E3 ubiquitin ligase protein (Williams et al., 2010, Genetics in Medicine). UBE3A-ATS has become a primary therapeutic target for Angelman syndrome, with pharmacological strategies focusing on the use of antisense oligonucleotides (ASOs) to bind and degrade the transcript. By reducing UBE3A-ATS levels, these therapies aim to reactivate the dormant paternal UBE3A gene, thereby restoring protein expression and potentially ameliorating the clinical symptoms of the disease (Milazzo et al., 2021, Molecular Therapy).

Other names

UBE3A-ASUBE3A antisense RNASNHG14LNC-UBE3A-ATSSmall nucleolar RNA host gene 14

Antisense oligonucleotide-mediated RNase H-dependent degradation of the antisense transcript to reactivate the silenced paternal UBE3A allele (Meng et al., 2015, Nature).