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Natural antisense transcripts.

ABSTRACT: Recent years have seen the increasing understanding of the crucial role of RNA in the functioning of the eukaryotic genome. These discoveries, fueled by the achievements of the FANTOM, and later GENCODE and ENCODE consortia, led to the recognition of the important regulatory roles of natural antisense transcripts (NATs) arising from what was previously thought to be 'junk DNA'. Roughly defined as non-coding regulatory RNA transcribed from the opposite strand of a coding gene locus, NATs are proving to be a heterogeneous group with high potential for therapeutic application. Here, we attempt to summarize the rapidly growing knowledge about this important non-coding RNA subclass.

SUBMITTER: Khorkova O

PROVIDER: S-EPMC4170719 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature

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Natural antisense transcripts.

Khorkova Olga O Myers Amanda J AJ Hsiao Jane J Wahlestedt Claes C

Human molecular genetics 20140516 R1

Recent years have seen the increasing understanding of the crucial role of RNA in the functioning of the eukaryotic genome. These discoveries, fueled by the achievements of the FANTOM, and later GENCODE and ENCODE consortia, led to the recognition of the important regulatory roles of natural antisense transcripts (NATs) arising from what was previously thought to be 'junk DNA'. Roughly defined as non-coding regulatory RNA transcribed from the opposite strand of a coding gene locus, NATs are prov ...[more]

PMID: 24838284

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Regulatory roles of natural antisense transcripts.

Project description:Mammalian genomes encode numerous natural antisense transcripts, but the function of these transcripts is not well understood. Functional validation studies indicate that antisense transcripts are not a uniform group of regulatory RNAs but instead belong to multiple categories with some common features. Recent evidence indicates that antisense transcripts are frequently functional and use diverse transcriptional and post-transcriptional gene regulatory mechanisms to carry out a wide variety of biological roles.

| S-EPMC2850559 | biostudies-literature

Natural antisense transcripts as drug targets.

Project description:The recent discovery of vast non-coding RNA-based regulatory networks that can be easily modulated by nucleic acid-based drugs has opened numerous new therapeutic possibilities. Long non-coding RNA, and natural antisense transcripts (NATs) in particular, play a significant role in networks that involve a wide variety of disease-relevant biological mechanisms such as transcription, splicing, translation, mRNA degradation and others. Currently, significant efforts are dedicated to harnessing these newly emerging NAT-mediated biological mechanisms for therapeutic purposes. This review will highlight the recent clinical and pre-clinical developments in this field and survey the advances in nucleic acid-based drug technologies that make these developments possible.

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Natural antisense transcripts of Trifolium repens dehydrins.

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Conserved expression of natural antisense transcripts in mammals.

Project description:BackgroundRecent studies had found thousands of natural antisense transcripts originating from the same genomic loci of protein coding genes but from the opposite strand. It is unclear whether the majority of antisense transcripts are functional or merely transcriptional noise.ResultsUsing the Affymetrix Exon array with a modified cDNA synthesis protocol that enables genome-wide detection of antisense transcription, we conducted large-scale expression analysis of antisense transcripts in nine corresponding tissues from human, mouse and rat. We detected thousands of antisense transcripts, some of which show tissue-specific expression that could be subjected to further study for their potential function in the corresponding tissues/organs. The expression patterns of many antisense transcripts are conserved across species, suggesting selective pressure on these transcripts. When compared to protein-coding genes, antisense transcripts show a lesser degree of expression conservation. We also found a positive correlation between the sense and antisense expression across tissues.ConclusionOur results suggest that natural antisense transcripts are subjected to selective pressure but to a lesser degree compared to sense transcripts in mammals.

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Epigenetic regulation of human cis-natural antisense transcripts.

Project description:Mammalian genomes encode numerous cis-natural antisense transcripts (cis-NATs). The extent to which these cis-NATs are actively regulated and ultimately functionally relevant, as opposed to transcriptional noise, remains a matter of debate. To address this issue, we analyzed the chromatin environment and RNA Pol II binding properties of human cis-NAT promoters genome-wide. Cap analysis of gene expression data were used to identify thousands of cis-NAT promoters, and profiles of nine histone modifications and RNA Pol II binding for these promoters in ENCODE cell types were analyzed using chromatin immunoprecipitation followed by sequencing (ChIP-seq) data. Active cis-NAT promoters are enriched with activating histone modifications and occupied by RNA Pol II, whereas weak cis-NAT promoters are depleted for both activating modifications and RNA Pol II. The enrichment levels of activating histone modifications and RNA Pol II binding show peaks centered around cis-NAT transcriptional start sites, and the levels of activating histone modifications at cis-NAT promoters are positively correlated with cis-NAT expression levels. Cis-NAT promoters also show highly tissue-specific patterns of expression. These results suggest that human cis-NATs are actively transcribed by the RNA Pol II and that their expression is epigenetically regulated, prerequisites for a functional potential for many of these non-coding RNAs.

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Pseudogenes as an alternative source of natural antisense transcripts.

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Natural Antisense Transcripts: Molecular Mechanisms and Implications in Breast Cancers.

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Natural antisense transcripts of UL123 packaged in human cytomegalovirus virions.

Project description:In this study, we demonstrated that antisense transcripts of human cytomegalovirus (HCMV) UL123, UL21.5 and cellular GAPDH genes were present in highly purified virions. These virion RNAs were delivered into the host cells upon infection, and de novo synthesized ones appeared in the infected cell at the immediate early stage. Although the sequence of UL123 antisense transcripts in virions is uncertain, we found that these transcripts in Towne-infected human fibroblasts had novel transcriptional start sites (TSSs) with various 5'-terminal deletions of open reading frame (ORF) 59. These findings not only provide new insight into the composition of HCMV virions but also reveal a possible viral strategy for initiating latent infection and switching between latent and productive infections.

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Natural antisense transcripts regulate the neuronal stress response and excitability.

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