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Ube3a-ATS
UBE3A-ATS/Ube3a-ATS (human/mouse), otherwise known as ubiquitin ligase E3A-ATS, is the name for the antisense DNA strand that is transcribed as part of a larger transcript called ''LNCAT'' (large non-coding antisense transcript) at the ''Ube3a'' locus. The ''Ube3a'' locus is imprinted and in the central nervous system expressed only from the maternal allele. Silencing of ''Ube3a'' on the paternal allele is thought to occur through the ''Ube3a-ATS'' part of ''LNCAT'', since non-coding antisense transcripts are often found at imprinted loci. The deletion and/or mutation of ''Ube3a'' on the maternal chromosome causes Angelman Syndrome (AS) and ''Ube3a-ATS'' may prove to be an important aspect in finding a therapy for this disease. While in patients with AS the maternal ''Ube3a'' allele is inactive, the paternal allele is intact but epigenetically silenced. If unsilenced, the paternal allele could be a source of active Ube3a protein in AS patients. Therefore, understanding the mechanisms of how ''Ube3a-ATS'' might be involved in silencing the paternal ''Ube3a'' may lead to new therapies for AS. This possibility has been demonstrated by a recent study where the drug topotecan, administered to mice suffering from AS, activated expression of the paternal ''Ube3a'' gene by lowering the transcription of ''Ube3a-ATS''.
==''LNCAT'' organization==
The human ''UBE3A-ATS'' is expressed as a part of ''LNCAT'' mainly from the paternal allele in the central nervous system (CNS).〔 The transcript is about 450 kbs long, starts at the U-exons and extends as far as ''UBE3A'' on the opposite strand, possibly beyond. The promoter for ''Snurf/Snrpn'' and the imprinting center are found in the U-exon region. The promoter region is imperative, as deletion of this area abolishes ''Ube3a-ATS'' transcription. Near the promoter is the PWS-IC and about 35 kbs upstream of the PWS-IC is the AS-IC. These two regions are thought to control the expression of the entire ''LNCAT'' strand. Starting at the promoter, the entire transcript can be transcribed and after transcription is further processed and spliced. Reviewed in ''Trends in Neurosci''.〔
Located next to the U-exon promoter region is ''Snrpn/Snurf'' which can be alternatively spliced into either ''Snrpn'' or ''Snurf'' in humans (in mice this remains as one bicistronic transcript). ''Snrpn'' codes for a protein of unknown function which localizes to the cell nucleus. ''Snurf'' codes for a small nuclear ribonucleoprotein. While most of these proteins are involved in splicing, the role of this particular protein is not yet known.〔 Downstream from ''Snrpn/Snurf'' and within its introns are sequences for several C/D box snoRNAs. Most C/D box snoRNAs function in non-mRNA methylation.〔 However, recently, one snoRNA on ''Ube3a-ATS'', SNORD 115, has been found to change the alternative splicing of the serotonin receptor 2C pre-mRNA. In addition, this snoRNA has the ability to change the splicing of five different mRNAs. Among the sequences for the snoRNAs is nested IPW (imprinted Prader-Willi), a non-coding region whose deletion is thought to cause Prader-Willi syndrome.
抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』
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