Natural antisense transcription from a comparative perspective

Piatek, Monica J.; Henderson, Victoria; Zynad, Hany S.; Werner, Andreas

doi:10.1016/j.ygeno.2016.05.004

Cited by 16 publications

(16 citation statements)

References 40 publications

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“… 11 Moreover, high gene locus-specific combinations of sense/antisense (S/AS) pairs make NATs promising precise therapeutic targets. 12 , 13 However, among the enormous amount of non-coding RNAs (ncRNAs), NATs are less studied compared with other types of ncRNA, especially another subclass of long non-coding RNA (lncRNA), long-intergenic non-coding RNAs (lincRNAs); 12 , 13 hence, the functional roles of the vast majority of NATs in CRC remain to be explored.…”

Section: Introductionmentioning

confidence: 99%

Increased expression of antisense lncRNA <em>SPINT1-AS1</em> predicts a poor prognosis in colorectal cancer and is negatively correlated with its sense transcript

Zhang

et al. 2018

OTT

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PurposeColorectal cancer (CRC) is a leading cause of cancer-associated mortality worldwide. Natural antisense transcripts (NATs) are pervasively expressed in human genome and have been confirmed to contribute to cancer progression. In our study, we aimed to investigate the expression and clinical pertinence of serine peptidase inhibitor, Kunitz type 1 antisense RNA1 (SPINT1-AS1) in CRC.Materials and methodsThe expression levels of SPINT1-AS1 and the corresponding sense transcript SPINT1 mRNA were analyzed in 150 pairs of CRC tissues and adjacent normal (AN) tissues, along with 45 pairs of preoperative and postoperative serum exosome samples by the strand-specific real-time quantitative polymerase chain reaction.ResultsCompared with AN tissues, the expression of SPINT1-AS1 was increased (P<0.001, 3.771 vs 0.980) in CRC tissues, while SPINT1 mRNA expression was decreased in CRC (P<0.001, 0.927 vs 1.165), and there was an obviously negative correlation between SPINT1-AS1 expression and its sense transcript (r=−0.701, P<0.001). SPINT1-AS1 yielded an area under the receiver operating characteristic curve value of 0.865 (95% confidence interval, 0.821–0.902) for discriminating CRC tissues from AN tissues. Moreover, high SPINT1-AS1 expression was correlated with regional lymph node metastasis (P<0.001), distant metastasis (P<0.001), and shorter relapse-free survival (RFS) time (P<0.001), and Cox regression analysis indicated that SPINT1-AS1 was an independent prognostic factor for RFS. Meanwhile, significant reduction of SPINT1-AS1 expression level (P=0.001) was observed in CRC serum exosomes after surgical resection.ConclusionSPINT1-AS1 is upregulated in CRC tissues and plays an essential role in CRC progression and prognosis. Thereby, SPINT1-AS1 may serve as a candidate prognostic biomarker and molecular therapy target for CRC.

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Section: Introductionmentioning

confidence: 99%

Increased expression of antisense lncRNA <em>SPINT1-AS1</em> predicts a poor prognosis in colorectal cancer and is negatively correlated with its sense transcript

Zhang

et al. 2018

OTT

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“…Several lines of independent evidence suggest that dsRNA formation is an essential step in an antisense mediated regulatory cascade [18, 22, 38]. Hence, the expression of complementary transcripts must be tightly coordinated to enable a timely interaction and also to avoid ectopic formation of dsRNA, an event that potentially triggers an antiviral response [39].…”

Section: Discussionmentioning

confidence: 99%

Ectopically expressed Slc34a2a sense-antisense transcripts cause a cerebellar phenotype in zebrafish embryos depending on RNA complementarity and Dicer

et al. 2017

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Natural antisense transcripts (NATs) are complementary to protein coding genes and potentially regulate their expression. Despite widespread occurrence of NATs in the genomes of higher eukaryotes, their biological role and mechanism of action is poorly understood. Zebrafish embryos offer a unique model system to study sense-antisense transcript interplay at whole organism level. Here, we investigate putative antisense transcript-mediated mechanisms by ectopically co-expressing the complementary transcripts during early zebrafish development. In zebrafish the gene Slc34a2a (Na-phosphate transporter) is bi-directionally transcribed, the NAT predominantly during early development up to 48 hours after fertilization. Declining levels of the NAT, Slc34a2a(as), coincide with an increase of the sense transcript. At that time, sense and antisense transcripts co-localize in the endoderm at near equal amounts. Ectopic expression of the sense transcript during embryogenesis leads to specific failure to develop a cerebellum. The defect is RNA-mediated and dependent on sense-antisense complementarity. Overexpression of a Slc34a2a paralogue (Slc34a2b) or the NAT itself had no phenotypic consequences. Knockdown of Dicer rescued the brain defect suggesting that RNA interference is required to mediate the phenotype. Our results corroborate previous reports of Slc34a2a-related endo-siRNAs in two days old zebrafish embryos and emphasize the importance of coordinated expression of sense-antisense transcripts. Our findings suggest that RNAi is involved in gene regulation by certain natural antisense RNAs.

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“…Pervasive bidirectional transcription may result in double-stranded RNA (dsRNA) formation due to complementary base pairing of sense and anti-sense transcripts (Piatek et al 2016).…”

Section: Ectopic Bidirectional Transcription At Zfp-1/dot-11 Enhancementioning

confidence: 99%

DOT1L suppresses nuclear RNAi originating from enhancer elements in Caenorhabditis elegans

Esse

Gushchanskaia

et al. 2018

Preprint

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Summary 7Methylation of histone H3 lysine 79 (H3K79) by DOT1L is associated with actively 8 transcribed genes. We have previously demonstrated that DOT-1.1, the Caenorhabditis 9 elegans DOT1L homologue, cooperates with the chromatin-binding protein ZFP-1 10 (homologue of the mammalian AF10) to negatively modulate transcription of highly and 11 widely expressed target genes. Also, zfp-1 deficiency has been associated with reduced 12 RNA interference (RNAi) response. In addition, in MLL-rearranged leukemia, H3K79 13 methylation at homeobox genes was shown to antagonize repressive chromatin marks. 14 Here, we connect these various manifestations of DOT1L function. We demonstrate that 15 DOT1L suppresses transcription at enhancers, thereby preventing double-stranded 16 RNA (dsRNA) formation and ectopic histone H3 lysine 9 (H3K9) methylation. Moreover, 17we show that lethality of dot-1.1 mutant worms is suppressed by mutations in the RNAi 18 pathway, suggesting ectopic activation of endogenous RNAi in the absence of DOT1L.

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Natural antisense transcription from a comparative perspective

Cited by 16 publications

References 40 publications

Increased expression of antisense lncRNA <em>SPINT1-AS1</em> predicts a poor prognosis in colorectal cancer and is negatively correlated with its sense transcript

Increased expression of antisense lncRNA <em>SPINT1-AS1</em> predicts a poor prognosis in colorectal cancer and is negatively correlated with its sense transcript

Ectopically expressed Slc34a2a sense-antisense transcripts cause a cerebellar phenotype in zebrafish embryos depending on RNA complementarity and Dicer

DOT1L suppresses nuclear RNAi originating from enhancer elements in Caenorhabditis elegans

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