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

Ubiquitin protein ligase E3A antisense transcript (UBE3A-ATS) is a long non-coding RNA (lncRNA) that mediates the genomic imprinting of the UBE3A gene within the central nervous system (NCBI Gene: 100133319). In neurons, UBE3A-ATS is expressed exclusively from the paternal allele and silences the paternal UBE3A gene through transcriptional interference, leaving the maternal copy as the sole source of functional UBE3A protein (Milazzo et al., 2021). Angelman syndrome occurs when the maternal UBE3A allele is lost or mutated, and because the paternal allele is silenced by UBE3A-ATS, the brain lacks essential UBE3A protein (Silva-Santos et al., 2015). Consequently, UBE3A-ATS has emerged as a primary therapeutic target for "unsilencing" the dormant paternal allele. Current clinical candidates, such as rugonersen and GTX-102, are antisense oligonucleotides (ASOs) designed to bind and promote the degradation of UBE3A-ATS, thereby restoring UBE3A expression in the brain (ClinicalTrials.gov: NCT04259281). While this approach is promising, therapeutic challenges include the need for precise titration to avoid UBE3A over-expression, which is associated with autism spectrum disorders.

Other names

UBE3A-ASSNHG14UBE3A antisense RNASmall nucleolar RNA host gene 14UBE3A-ATS lncRNA

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