Ube3a-ATS
The Ube3a-ATS, or UBE3A-Antisense Transcript, refers to the antisense transcript of the UBE3A gene. UBE3A (Ubiquitin Protein Ligase E3A) encodes an E3 ubiquitin ligase enzyme responsible for tagging proteins with ubiquitin, marking them for degradation or altering their function. This enzyme plays a crucial role in synaptic plasticity and neuronal development, particularly in the brain.
The Ube3a-ATS is a long non-coding RNA (lncRNA) transcribed from the opposite strand of the UBE3A gene. Importantly, the Ube3a-ATS includes the coding sequence of the paternal UBE3A allele in neurons. It's implicated in regulating the expression of UBE3A in a parent-of-origin-specific manner, a phenomenon known as genomic imprinting. Specifically, in neurons, the maternal UBE3A allele is actively transcribed, while the paternal allele is usually silenced due to the expression of the Ube3a-ATS.
The Ube3a-ATS is complex and spans a significant region of chromosome 15q11.2, often extending from the SNRPN (Small Nuclear Ribonucleoprotein Polypeptide N) gene through to the UBE3A gene. Its expression pattern is tissue-specific and developmentally regulated.
Disruptions in the Ube3a-ATS are associated with Angelman syndrome (AS) and Prader-Willi syndrome (PWS), two distinct neurodevelopmental disorders caused by defects in the 15q11.2 region. In Angelman syndrome, the maternal copy of UBE3A is either deleted or mutated, leading to a loss of functional UBE3A protein. While mutations directly affecting the UBE3A gene account for some AS cases, a significant proportion arise from defects in the imprinting mechanism. These defects often involve deletions or mutations in the SNRPN locus, which disrupts the expression of the Ube3a-ATS, leading to silencing of the maternal UBE3A allele in neurons (effectively resulting in no functional UBE3A protein in the brain). In Prader-Willi syndrome, the paternal copy of the SNRPN/Ube3a-ATS region is deleted or silenced, leading to a lack of expression of paternally expressed genes in that region.