Natural antisense transcript stabilizes inducible nitric oxide synthase messenger RNA in rat hepatocytes

Matsui, Kosuke; Nishizawa, Mikio; Ozaki, Takashi; Kimura, Tetsuya; Hashimoto, Iwao; Yamada, Masakazu; Kaibori, Masaki; Kamiyama, Yasuo; Ito, Seiji; Okumura, Tadayoshi

doi:10.1002/hep.22036

Cited by 155 publications

(228 citation statements)

References 41 publications

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“…More than 5% of human genes contain 50-150 nt of AU-rich elements (AREs) in their 39-UTRs, which recruit RNA-binding proteins such as AUF1 and lead to destabilization of the transcript through deadenylation, decapping, and degradation via the action of cellular machineries such as the exosome (Barreau et al 2006). A NAT produced from the 39-UTR of iNOS (inducible nitric oxide synthase) has been found to interact with its sense counterpart and with HuR, an AREbinding factor that increases the stability of ARE-containing transcripts (Matsui et al 2008). This suggests a potential mechanism whereby a NAT helps stabilize its sense counterpart by aiding in the recruitment of stabilizing factors.…”

Section: Transcript or Act Of Transcription?mentioning

confidence: 99%

Long Noncoding RNAs: Past, Present, and Future

2013

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Long noncoding RNAs (lncRNAs) have gained widespread attention in recent years as a potentially new and crucial layer of biological regulation. lncRNAs of all kinds have been implicated in a range of developmental processes and diseases, but knowledge of the mechanisms by which they act is still surprisingly limited, and claims that almost the entirety of the mammalian genome is transcribed into functional noncoding transcripts remain controversial. At the same time, a small number of well-studied lncRNAs have given us important clues about the biology of these molecules, and a few key functional and mechanistic themes have begun to emerge, although the robustness of these models and classification schemes remains to be seen. Here, we review the current state of knowledge of the lncRNA field, discussing what is known about the genomic contexts, biological functions, and mechanisms of action of lncRNAs. We also reflect on how the recent interest in lncRNAs is deeply rooted in biology's longstanding concern with the evolution and function of genomes.T HE past several years have witnessed a steep rise of interest in the study of lncRNAs. Almost on a weekly basis, it seems that a new lncRNA is found to be up-or downregulated in a particular disease, or a new class of noncoding transcripts is uncovered by a transcriptomic study, or a new article heralds a paradigm shift that lncRNAs will bring to our understanding of biology. Without a doubt, the advent of sensitive, high-throughput genomic technologies such as microarrays and next-generation sequencing (NGS) has resulted in an unprecedented ability to detect novel transcripts, the vast majority of which seem not to be derived from annotated protein-coding genes. Despite this explosion of data, however, surprisingly little is known about how lncRNAs function, how many different types of lncRNAs exist, or even whether most of them carry biological significance.In this review, we focus on recently discovered lncRNAs of .200 nt, place these new discoveries in historical context, and outline areas where additional work is needed. The review does not cover "classic" ncRNAs such as ribosomal (r) RNAs, ribozymes, transfer (t)RNAs, small nuclear (sn)RNAs, small nucleolar (sno)RNAs, and telomere-associated RNAs (TERC, TERRA); nor does it cover small ncRNAs such as microRNAs (miRNAs), endogenous small interfering (endo-si)RNAs that participate in RNA interference (RNAi), and Piwi-associated (pi)RNAs. We refer readers to the many

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Section: Transcript or Act Of Transcription?mentioning

confidence: 99%

Long Noncoding RNAs: Past, Present, and Future

2013

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“…www.cell-research.com | Cell Research Wen-Yu Su et al 1377 npg data demonstrated that the DHPS overlapping 3′UTR mediated the regulation of WDR83 expression through antisense pairing, which supported the notion that although the 3′UTR had no coding potential, it exerted a biological effect [17]. The luciferase reporter assay showed that the WDR83 3′UTR-containing construct induced a 24.4% increase in luciferase activity in cells that were cotransfected with the DHPS 3′UTR plasmid (P = 0.0020), and the WDR83 full-length construct also showed an increase in luciferase activity (P = 0.0310).…”

Section: Dhps Mrna Regulated Wdr83 Through Antisense Overlappingmentioning

confidence: 89%

Bidirectional regulation between WDR83 and its natural antisense transcript DHPS in gastric cancer

Su¹,

Cui

et al. 2012

Cell Res

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Natural antisense transcripts (NATs) exist ubiquitously in mammalian genomes and play roles in the regulation of gene expression. However, both the existence of bidirectional antisense RNA regulation and the possibility of proteincoding genes that function as antisense RNAs remain speculative. Here, we found that the protein-coding gene, deoxyhypusine synthase (DHPS), as the NAT of WDR83, concordantly regulated the expression of WDR83 mRNA and protein. Conversely, WDR83 also regulated DHPS by antisense pairing in a concordant manner. WDR83 and DHPS were capable of forming an RNA duplex at overlapping 3′ untranslated regions and this duplex increased their mutual stability, which was required for the bidirectional regulation. As a pair of protein-coding cis-sense/antisense transcripts, WDR83 and DHPS were upregulated simultaneously and correlated positively in gastric cancer (GC), driving GC pathophysiology by promoting cell proliferation. Furthermore, the positive relationship between WDR83 and DHPS was also observed in other cancers. The bidirectional regulatory relationship between WDR83 and DHPS not only enriches our understanding of antisense regulation, but also provides a more complete understanding of their functions in tumor development.

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“…Among them, early response genes [20] , such as inducible nitric oxide synthase (iNOS), proinflammatory cytokines [e.g., tumor necrosis factor-alpha (TNF-alpha)], and chemokines, are intimately involved in the pathophysiology of inflammation and infection. In the presence of interleukin 1beta, iNOS asRNA interacts with and stabilizes iNOS mRNA [21] . Single-stranded sense oligodeoxyribonucleotides corresponding to the iNOS mRNA sequence decrease iNOS mRNA levels by interfering with mRNA-asRNA interactions [21] .…”

Section: Inflammation and Infectionmentioning

confidence: 99%

“…In the presence of interleukin 1beta, iNOS asRNA interacts with and stabilizes iNOS mRNA [21] . Single-stranded sense oligodeoxyribonucleotides corresponding to the iNOS mRNA sequence decrease iNOS mRNA levels by interfering with mRNA-asRNA interactions [21] . This method is referred to as natural antisense transcript-targeted regulation (NATRE) technology [22] .…”

Section: Inflammation and Infectionmentioning

confidence: 99%

RNA Networks that Regulate mRNA Expression and their Potential as Drug Targets

Nishizawa

Kimura

2015

RNA Dis

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Natural antisense transcripts (asRNAs) transcribed from eukaryotic genes are primarily long transcripts that do not code for proteins. Transcriptome analyses have revealed that asRNAs exhibit diverse functional roles in the regulation of gene expression. In the case of inducible genes, asRNAs epigenetically affect their expression or post-transcriptionally affect stability and translatability of their mRNAs. Many low-copy-number asRNAs regulate the expression levels of mRNAs through cis-controlling elements in the mRNA in concert with trans-acting factors, such as RNA-binding proteins and microRNAs. Recently, a competitive endogenous RNA (ceRNA) hypothesis was postulated as the basis of a functional network, comprising mRNAs, asRNAs, and microRNAs. This network finely tunes mRNA expression by common microRNA-responsive elements being present among mRNAs and asRNAs, permitting the redirection of microRNAs between the two. Examples of the ceRNA-mediated cross-regulation of mRNA expression are observed in the phosphatase and tensin homolog mRNA network and the interferon-alpha1 mRNA network. In such regulatory RNA networks, an mRNA, its corresponding asRNAs (high specificity), microRNAs (low specificity), and RNA-binding proteins mutually interact. Both asRNAs and microRNAs are involved in the pathogenesis or pathophysiology of various diseases, such as cancer, inflammation, and infection. Simple disruption of an asRNA or a microRNA can often show off-target effects due to complicated interactions inside and outside the regulatory RNA networks. Therefore, drugs that target asRNAs should be developed to minimize off-target effects and to target interactions that are dysregulated in disease.

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Natural antisense transcript stabilizes inducible nitric oxide synthase messenger RNA in rat hepatocytes

Cited by 155 publications

References 41 publications

Long Noncoding RNAs: Past, Present, and Future

Long Noncoding RNAs: Past, Present, and Future

Bidirectional regulation between WDR83 and its natural antisense transcript DHPS in gastric cancer

RNA Networks that Regulate mRNA Expression and their Potential as Drug Targets

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