Dynamic developmental regulation of the large non-coding RNA associated with the mouse 7C imprinted chromosomal region.

The mouse ortholog of the Prader-Willi/Angelman syndrome imprinted domain contains several paternal-specific transcripts and the maternally expressed gene encoding ubiquitin protein ligase E3A (Ube3a). A Large paternal Non-Coding RNA, encompassing Snurf-Snrpn exons and the Ube3a Antisense Transcript (Ube3a-ATS), has been recently characterized and named here LNCAT. Potential roles of LNCAT in imprinting, gene regulation, and disease are likely but have not been investigated.

Maternal disruption of Ube3a leads to increased expression of Ube3a-ATS in trans.

Angelman syndrome (AS) is a neurogenetic disorder characterized by severe mental retardation, 'puppet-like' ataxic gait with jerky arm movements, seizures, EEG abnormalities, hyperactivity and bouts of inappropriate laughter. Individuals with AS fail to inherit a normal active maternal copy of the gene encoding ubiquitin protein ligase E3A (UBE3A). UBE3A is transcribed predominantly from the maternal allele in brain, but is expressed from both alleles in most other tissues.

Regulation of the large (approximately 1000 kb) imprinted murine Ube3a antisense transcript by alternative exons upstream of Snurf/Snrpn.

Most cases of Angelman syndrome (AS) result from loss or inactivation of ubiquitin protein ligase 3A (UBE3A), a gene displaying maternal-specific expression in brain. Epigenetic silencing of the paternal UBE3A allele in brain appears to be mediated by a non-coding UBE3A antisense (UBE3A-ATS). In human, UBE3A-ATS extends approximately 450 kb to UBE3A from the small nuclear ribonucleoprotein N (SNURF/SNRPN) promoter region that contains a cis-acting imprinting center (IC).