Identification of novel endogenous antisense transcripts by DNA microarray analysis targeting complementary strand of annotated genes

Numata, Koji; Osada, Yuko; Okada, Yuki; Saito, Rintaro; Hiraiwa, Noriko; Nakaoka, Hajime; Yamamoto, Naoyuki; Watanabe, Kazufumi; Okubo, Kazue; Kohama, Chihiro; Kanai, Akio; Abe, Kuniya; Kiyosawa, Hidenori

doi:10.1186/1471-2164-10-392

Cited by 13 publications

(19 citation statements)

References 51 publications

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“…31 Today endogenous antisense transcription is recognized as pervasive and as an integral cellular activity. 32,33,34,35 The regulatory potential of antisense transcripts was immediately recognized, 36 and their main activity was initially linked to interference with protein translation. 37,38 However, more recent observations suggest an important role of natural antisense transcripts in the regulation of gene transcription by epigenetic modification of chromatin.…”

Section: Discussionmentioning

confidence: 99%

An Algorithm for Generating Small RNAs Capable of Epigenetically Modulating Transcriptional Gene Silencing and Activation in Human Cells

Ackley

Lenox

Stapleton

et al. 2013

Molecular Therapy - Nucleic Acids

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Small noncoding antisense RNAs (sasRNAs) guide epigenetic silencing complexes to target loci in human cells and modulate gene transcription. When these targeted loci are situated within a promoter, long-term, stable epigenetic silencing of transcription can occur. Recent studies suggest that there exists an endogenous form of such epigenetic regulation in human cells involving long noncoding RNAs. In this article, we present and validate an algorithm for the generation of highly effective sasRNAs that can mimic the endogenous noncoding RNAs involved in the epigenetic regulation of gene expression. We validate this algorithm by targeting several oncogenes including AKT-1, c-MYC, K-RAS, and H-RAS. We also target a long antisense RNA that mediates the epigenetic repression of the tumor suppressor gene DUSP6, silenced in pancreatic cancer. An algorithm that can efficiently design small noncoding RNAs for the epigenetic transcriptional silencing or activation of specific genes has potential therapeutic and experimental applications.

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Section: Discussionmentioning

confidence: 99%

An Algorithm for Generating Small RNAs Capable of Epigenetically Modulating Transcriptional Gene Silencing and Activation in Human Cells

Ackley

Lenox

Stapleton

et al. 2013

Molecular Therapy - Nucleic Acids

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“…It will be of interest to determine whether these sense-antisense (S/AS) pairs are conserved in human, especially as a very short (focal) region of genome amplification in human chromosome 12q23.1 that only contains the genes ELK3 and PCTK2 occurs at a significantly high frequency among 3131 cancer specimens ((Beroukhim et al, 2010); http://www.broadinstitute.org/tumorscape). A large proportion of S/AS pairs are co-expressed (Ge et al, 2008; Katayama et al, 2005; Sun et al, 2005) and bioinformatic studies have found many examples of exon-overlapping S/AS pairs conserved between mouse and human (Numata et al, 2007; Numata et al, 2009; Okada et al, 2008). This suggests that gene expression can be regulated by the formation of S/AS perfectly complementary double-stranded RNA (dsRNA; (Numata et al, 2007; Sun et al, 2005; Werner et al, 2009)), the latter being detectable by RNase protection assays (Munroe and Zhu, 2006).…”

Section: Discussionmentioning

confidence: 99%

The expression of ELK transcription factors in adult DRG: Novel isoforms, antisense transcripts and upregulation by nerve damage

Kerr

Pintzas²,

Holmes³

et al. 2010

Molecular and Cellular Neuroscience

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ELK transcription factors are expressed in brain, but it is unknown whether they are expressed in the peripheral nervous system. We show by RT-PCR that the previously described Elk1, Elk3/Elk3b/Elk3c and Elk4 mRNAs are expressed in adult dorsal root ganglia (DRG), together with the novel alternatively spliced isoforms Elk1b, Elk3d and Elk4c/Elk4d/Elk4e. These isoforms are also expressed in brain, heart, kidney and testis. In contrast to Elk3 protein, the novel Elk3d isoform is cytoplasmic, fails to bind ETS binding sites and yet can activate transcription by an indirect mechanism. The Elk3 and Elk4 genes are overlapped by co-expressed Pctk2 and Mfsd4 genes, respectively, with the potential formation of Elk3/Pctaire2 and Elk4/Mfsd4 sense-antisense mRNA heteroduplexes. After peripheral nerve injury the Elk3 mRNA isoforms are each upregulated ~2.3-fold in DRG (P<0.005), whereas the natural antisense Pctaire2 isoforms show only a small increase (21%, P<0.01) and Elk1 and Elk4 mRNAs are unchanged.

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“…In this way, we were able to detect the expression of novel antisense RNAs, which were not detected by using cDNA sequences [11]. These AFAS probes were spotted onto microarray slides and used in our microarray platform to generate expression data for the analysis of antisense transcripts.…”

Section: Introductionmentioning

confidence: 99%

Comprehensive expressional analyses of antisense transcripts in colon cancer tissues using artificial antisense probes

et al. 2011

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BackgroundRecent studies have identified thousands of sense-antisense gene pairs across different genomes by computational mapping of cDNA sequences. These studies have shown that approximately 25% of all transcriptional units in the human and mouse genomes are involved in cis-sense-antisense pairs. However, the number of known sense-antisense pairs remains limited because currently available cDNA sequences represent only a fraction of the total number of transcripts comprising the transcriptome of each cell type.MethodsTo discover novel antisense transcripts encoded in the antisense strand of important genes, such as cancer-related genes, we conducted expression analyses of antisense transcripts using our custom microarray platform along with 2376 probes designed specifically to detect the potential antisense transcripts of 501 well-known genes suitable for cancer research.ResultsUsing colon cancer tissue and normal tissue surrounding the cancer tissue obtained from 6 patients, we found that antisense transcripts without poly(A) tails are expressed from approximately 80% of these well-known genes. This observation is consistent with our previous finding that many antisense transcripts expressed in a cell are poly(A)-. We also identified 101 and 71 antisense probes displaying a high level of expression specifically in normal and cancer tissues respectively.ConclusionOur microarray analysis identified novel antisense transcripts with expression profiles specific to cancer tissue, some of which might play a role in the regulatory networks underlying oncogenesis and thus are potential targets for further experimental validation. Our microarray data are available at http://www.brc.riken.go.jp/ncrna2007/viewer-Saito-01/index.html.

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Identification of novel endogenous antisense transcripts by DNA microarray analysis targeting complementary strand of annotated genes

Cited by 13 publications

References 51 publications

An Algorithm for Generating Small RNAs Capable of Epigenetically Modulating Transcriptional Gene Silencing and Activation in Human Cells

An Algorithm for Generating Small RNAs Capable of Epigenetically Modulating Transcriptional Gene Silencing and Activation in Human Cells

The expression of ELK transcription factors in adult DRG: Novel isoforms, antisense transcripts and upregulation by nerve damage

Comprehensive expressional analyses of antisense transcripts in colon cancer tissues using artificial antisense probes

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