Abstract
BackgroundSeveral high-throughput searches for ppotential natural antisense transcripts (NATs) have been performed recently, but most of the reports were focused on cis type. A thorough in silico analysis of human transcripts will help expand our knowledge of NATs.ResultsWe have identified 568 NATs from human RefSeq RNA sequences. Among them, 403 NATs are reported for the first time, and at least 157 novel NATs are trans type. According to the pairing region of a sense and antisense RNA pair, hNATs are divided into 6 classes, of which about 87% involve 5' or 3' UTR sequences, supporting the regulatory role of UTRs. Among a total of 535 NAT pairs related with splice variants, 77.4% (414/535) have their pairing regions affected or completely eliminated by alternative splicing, suggesting significant relationship of alternative splicing and antisense-directed regulation. The extensive occurrence of splice variants in hNATs and other multiple pairing patterns results in a one-to-many relationship, allowing the formation of complex regulation networks. Based on microarray data from Stanford Microarray Database, two hNAT pairs were found to display significant inverse expression patterns before and after insulin injection.ConclusionNATs might carry out more extensive and complex functions than previously thought. Combined with endogenous micro RNAs, hNATs could be regarded as a special group of transcripts contributing to the complex regulation networks.
Highlights
Several high-throughput searches for ppotential natural antisense transcripts (NATs) have been performed recently, but most of the reports were focused on cis type
We found limited human NATs (hNATs) compared to previous reports, sequence accession number matching showed that 403 out of the 568 NAT pairs did not appear in any of the published data sets [10,11,12,13], indicating that antisense regulation may be even more widespread in the mammalian genome than appreciated previously
Through a systematic analysis of hNATs using RefSeq dataset, we identified 568 hNATs
Summary
Several high-throughput searches for ppotential natural antisense transcripts (NATs) have been performed recently, but most of the reports were focused on cis type. A thorough in silico analysis of human transcripts will help expand our knowledge of NATs. Natural antisense transcripts (NATs) are endogenous ones that exhibit complementary sequences to transcripts of a known function, or sense transcripts. It has been shown that NATs could perform two non-exclusive major functions: template for translation and regulation of sense gene expression, and the latter (page number not for citation purposes). As NATs seemed to exist so extensively, independent genome-wide searches for potential NATs were performed recently with data from RefSeq, UniGene or some specially constructed EST database. Due to differences in data sources and/or criteria used in searches, the number of reported human NATs (hNATs) varies greatly, from hundreds [10,11] to thousands [12,13]
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