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Wiley Interdisciplinary Reviews. RNA Mar 2018Antisense transcription is a widespread phenomenon in mammalian genomes, leading to production of RNAs molecules referred to as natural antisense transcripts (NATs).... (Review)
Review
Antisense transcription is a widespread phenomenon in mammalian genomes, leading to production of RNAs molecules referred to as natural antisense transcripts (NATs). NATs apply diverse transcriptional and post-transcriptional regulatory mechanisms to carry out a wide variety of biological roles that are important for the normal functioning of living cells, but their dysfunctions can be associated with human diseases. In this review, we attempt to provide a molecular basis for the involvement of NATs in the etiology of human disorders such as cancers and neurodegenerative and cardiovascular diseases. We also discuss the pros and cons of oligonucleotide-based therapies targeted against NATs, and we comment on state-of-the-art progress in this promising area of clinical research. WIREs RNA 2018, 9:e1461. doi: 10.1002/wrna.1461 This article is categorized under: RNA in Disease and Development > RNA in Disease Regulatory RNAs/RNAi/Riboswitches > Regulatory RNAs RNA Interactions with Proteins and Other Molecules > Small Molecule-RNA Interactions.
Topics: Animals; Disease; Humans; Molecular Targeted Therapy; RNA, Antisense; Transcription, Genetic
PubMed: 29341438
DOI: 10.1002/wrna.1461 -
Essays in Biochemistry 2013NATs (natural antisense transcripts) are widespread in eukaryotic genomes. Experimental evidence indicates that sense and antisense transcripts interact, suggesting a... (Review)
Review
NATs (natural antisense transcripts) are widespread in eukaryotic genomes. Experimental evidence indicates that sense and antisense transcripts interact, suggesting a role for NATs in the regulation of gene expression. On the other hand, the transcription of a gene locus in both orientations and RNA hybrid formation can also lead to transcriptional interference, trigger an immune response or induce gene silencing. Tissue-specific expression of NATs and the compartmentalization of cells ensure that the regulatory impact of NATs prevails. Consequently, NATs are now acknowledged as important modulators of gene expression. New mechanisms of action and important biological roles of NATs keep emerging, making regulatory RNAs an exciting and quickly moving area of research.
Topics: Animals; Chromatin; Gene Expression Regulation; Humans; Pharmaceutical Preparations; RNA Editing; RNA Interference; RNA, Antisense
PubMed: 23829529
DOI: 10.1042/bse0540091 -
Annual Review of Genetics 2010Antisense RNAs encoded on the DNA strand opposite another gene have the potential to form extensive base-pairing interactions with the corresponding sense RNA. Unlike... (Review)
Review
Antisense RNAs encoded on the DNA strand opposite another gene have the potential to form extensive base-pairing interactions with the corresponding sense RNA. Unlike other smaller regulatory RNAs in bacteria, antisense RNAs range in size from tens to thousands of nucleotides. The numbers of antisense RNAs reported for different bacteria vary extensively, but hundreds have been suggested in some species. If all of these reported antisense RNAs are expressed at levels sufficient to regulate the genes encoded opposite them, antisense RNAs could significantly impact gene expression in bacteria. Here, we review the evidence for these RNA regulators and describe what is known about the functions and mechanisms of action for some of these RNAs. Important considerations for future research as well as potential applications are also discussed.
Topics: Bacteria; Gene Expression Regulation, Bacterial; RNA, Antisense; RNA, Bacterial
PubMed: 20707673
DOI: 10.1146/annurev-genet-102209-163523 -
RNA Biology Jan 2021Here, we describe SR7, a dual-function antisense RNA encoded on the chromosome. This RNA was earlier described as SigB-dependent regulatory RNA S1136 and reported to...
Here, we describe SR7, a dual-function antisense RNA encoded on the chromosome. This RNA was earlier described as SigB-dependent regulatory RNA S1136 and reported to reduce the amount of the small ribosomal subunit under ethanol stress. We found that the 5' portion of SR7 encodes a small protein composed of 39 amino acids which we designated SR7P. It is translated from a 185 nt SigB-dependent mRNA under five different stress conditions and a longer SigB-independent RNA constitutively. About three-fold higher amounts of SR7P were detected in cells exposed to salt, ethanol, acid or heat stress. Co-elution experiments with SR7P and Far-Western blotting demonstrated that SR7P interacts with the glycolytic enzyme enolase. Enolase is a scaffolding component of the degradosome where it interacts with RNase Y and phosphofructokinase PfkA. We found that SR7P increases the amount of RNase Y bound to enolase without affecting PfkA. RNA does not bridge the SR7P-enolase-RNase Y interaction. -degradation assays with the known RNase Y substrates and mRNA revealed enhanced enzymatic activity of enolase-bound RNase Y in the presence of SR7P. Northern blots showed a major effect of enolase and a minor effect of SR7P on the half-life of mRNA indicating a fine-tuning role of SR7P in RNA degradation.
Topics: Bacillus subtilis; Bacterial Proteins; Conserved Sequence; DNA, Intergenic; Gene Expression Regulation, Bacterial; Phosphopyruvate Hydratase; Protein Binding; RNA Stability; RNA, Antisense; RNA, Bacterial; RNA, Messenger; Stress, Physiological
PubMed: 32752915
DOI: 10.1080/15476286.2020.1798110 -
European Journal of Histochemistry : EJH Sep 2022Long non-coding RNA WAC antisense RNA 1 (lncRNA WAC-AS1) is involved in the replication of the hepatitis B virus (HBV). The purpose of this study was to determine its...
Long non-coding RNA WAC antisense RNA 1 (lncRNA WAC-AS1) is involved in the replication of the hepatitis B virus (HBV). The purpose of this study was to determine its functions and specific mechanism. The levels of lncRNA WAC-AS1, RNA (miR)-192-5p and were examined in serum of HBV-infected patients and in HepG2.2.15 cells using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and Western blotting. Using the database starBase, the target binding sites of lncRNA WAC-AS1 and miR-192-5p were predicted and confirmed by dual-luciferase reporter assay and RNA pull-down assay. The expression of pgRNA and HBV DNA was determined by qRT-PCR, while the levels of HBeAg and HBsAg were measured by enzyme-linked immunosorbent assay (ELISA). Using laser scanning confocal microscopy, the light chain 3 (LC3) expression was analyzed. qRT-PCR and Western blotting were used to assess the expression of beclin-1, p62, and LC3I/II. Overexpression of lncRNA WAC-AS1, upregulation of ATG7. and downregulation of miR-192-5p were observed in the serum of HBV-infected patients and the in vitro model. miR-192-5p directly targets lncRNA WAC-AS1. LncRNA WAC-AS1 was downregulated in lncRNA WAC-AS1-shRNA‒transfected cells. miR-192-5p was upregulated in lncRNA WAC-AS1-shRNA-transfected cells and downregulated in cells transfected with a miR-192-5p inhibitor. In HepG2 2.15 cells, the downregulation of lncRNA WAC-AS1 inhibited HBV replication and autophagy. In contrast, the miR-192-5p inhibitor-transfected group exhibited the opposite results, and ATG7 overexpression reversed the effects of miR-192-5p mimic or lncRNA WAC-AS1-shRNA on HBV replication and cell autophagy. Our findings indicate that lncRNA WAC-AS1 regulates HBV replication by reinforcing the autophagy induced by miR-192-5p/ATG7. Consequently, lncRNA WAC-AS1 may serve as a therapeutically-promising target in HBV patients.
Topics: Adaptor Proteins, Signal Transducing; Autophagy; Autophagy-Related Protein 7; Cell Line, Tumor; Hepatitis B; Hepatitis B virus; Humans; MicroRNAs; RNA, Antisense; RNA, Long Noncoding; RNA, Small Interfering; Virus Replication
PubMed: 36053263
DOI: 10.4081/ejh.2022.3438 -
Advanced Drug Delivery Reviews Jun 2015Synthetic, complementary DNA single strands and short interfering RNA double strands have been found to inhibit the expression of animal, plant, and viral genes in... (Review)
Review
Synthetic, complementary DNA single strands and short interfering RNA double strands have been found to inhibit the expression of animal, plant, and viral genes in cells, animals, and patients, in a dose dependent and sequence specific manner. DNAs and RNAs, however, are readily digested in biological systems. Hence, chemists are obliged to design and synthesize nuclease-resistant analogs of normal DNA (Fig. 1).
Topics: Animals; DNA, Antisense; Genetic Therapy; Humans; RNA Interference; RNA, Antisense
PubMed: 25912659
DOI: 10.1016/j.addr.2015.04.012 -
Hfq-Antisense RNA I Binding Regulates RNase E-Dependent RNA Stability and ColE1 Plasmid Copy Number.International Journal of Molecular... Apr 2024The mechanisms and consequences of gene regulation by Hfq on -encoded small RNAs (sRNAs) have been well studied and documented. Recent employment of Genomic SELEX to...
The mechanisms and consequences of gene regulation by Hfq on -encoded small RNAs (sRNAs) have been well studied and documented. Recent employment of Genomic SELEX to search for Hfq-binding motifs has indicated that Hfq might frequently regulate gene expression controlled by -antisense RNAs. Here, we use the classic ColE1 plasmid antisense RNA-based regulation model (i.e., RNA I) to study the role of Hfq in controlling antisense regulatory functions. We show that Hfq exhibits a high binding affinity for RNA I and that binding limits RNase E cleavage, thereby stabilizing RNA I and reducing the plasmid copy number. Full-length RNA I displays a binding affinity for Hfq in the sub-micromolar range. In vivo overexpression of Hfq prolongs RNA I stability and reduces the ColE1 plasmid copy number, whereas deletion of reduces RNA I stability and increases the plasmid copy number. RNA I predominantly binds to the proximal face of Hfq and exhibits competitive ability against a chromosome-borne proximal face-bound sRNA (DsrA) for Hfq binding. Through its strong promoter and high gene dosage features, plasmid-encoded antisense RNA I results in high RNA I expression, so it may antagonize the effects of -encoded RNAs in controlling target gene expression.
Topics: RNA, Antisense; DNA Copy Number Variations; Plasmids; RNA Stability; Endoribonucleases
PubMed: 38612765
DOI: 10.3390/ijms25073955 -
Bioengineered Apr 2022Endometriosis is an estrogen-dependent chronic gynecological syndrome. Recent studies have shown that long non-coding RNAs participate in the pathogenesis and...
Long non-coding RNA DHRS4 antisense RNA 1 inhibits ectopic endometrial cell proliferation, migration, and invasion in endometriosis by regulating microRNA-139-5p expression.
Endometriosis is an estrogen-dependent chronic gynecological syndrome. Recent studies have shown that long non-coding RNAs participate in the pathogenesis and development of endometriosis. This study aimed to explore the mechanisms of DHRS4 antisense RNA 1 (DHRS4-AS1) in endometriosis. Dual-luciferase reporter assays were conducted to determine the relationship between DHRS4-AS1, microRNA (miR)-139-5p, and arrestin domain-containing 3 (ARRDC3). Furthermore, the expression of DHRS4-AS1 and miR-139-5p in ectopic endometrial stromal cells (EC-ESCs) and endometriosis tissues was examined using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Additionally, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT), flow cytometry, and Transwell assays were performed to evaluate the proliferation, apoptosis, and migration and invasion of EC-ESCs, respectively. Western blotting and RT-qPCR were further utilized to determine cleaved-Caspase 3, Caspase 3, and matrix metalloproteinase 9 (MMP-9) expression levels. Compared with the EN group, DHRS4-AS1 levels were lower and miR-139-5p levels were higher in EC-ESCs and tissues obtained from patients with endometriosis. Functional assays validated that DHRS4-AS1 targets miR-139-5p, with ARRDC3 being a downstream target of miR-139-5p. Rescue experiments demonstrated that DHRS4-AS1 inhibited EC-ESC proliferation, migration, and invasion, but promoted apoptosis, by targeting miR-139-5p in endometriosis. cleaved-Caspase3 expression level and the cleaved-Caspase 3/Caspase 3 ratio increased, while the expression levels of MMP-9 decreased, after transfection with DHRS4-AS1 overexpression plasmids; however, the effects induced by DHRS4-AS1 overexpression could be partially reversed by co-transfection with the miR-139-5p mimic. The current study demonstrates that the DHRS4-AS1/miR-139-5p/ARRDC3 axis participates in the regulation of EC-ESC function.
Topics: Caspase 3; Cell Line, Tumor; Cell Movement; Cell Proliferation; Endometriosis; Female; Humans; Matrix Metalloproteinase 9; MicroRNAs; Oxidoreductases; RNA, Antisense; RNA, Long Noncoding
PubMed: 35414313
DOI: 10.1080/21655979.2022.2060781 -
Nature Communications Aug 2022Although antisense transcription is a widespread event in the mammalian genome, double-stranded RNA (dsRNA) formation between sense and antisense transcripts is very...
Although antisense transcription is a widespread event in the mammalian genome, double-stranded RNA (dsRNA) formation between sense and antisense transcripts is very rare and mechanisms that control dsRNA remain unknown. By characterizing the FGF-2 regulated transcriptome in normal and cancer cells, we identified sense and antisense transcripts IER3 and IER3-AS1 that play a critical role in FGF-2 controlled oncogenic pathways. We show that IER3 and IER3-AS1 regulate each other's transcription through HnRNPK-mediated post-transcriptional regulation. HnRNPK controls the mRNA stability and colocalization of IER3 and IER3-AS1. HnRNPK interaction with IER3 and IER3-AS1 determines their oncogenic functions by maintaining them in a single-stranded form. hnRNPK depletion neutralizes their oncogenic functions through promoting dsRNA formation and cytoplasmic accumulation. Intriguingly, hnRNPK loss-of-function and gain-of-function experiments reveal its role in maintaining global single- and double-stranded RNA. Thus, our data unveil the critical role of HnRNPK in maintaining single-stranded RNAs and their physiological functions by blocking RNA-RNA interactions.
Topics: Animals; Fibroblast Growth Factor 2; Gene Expression Regulation; Mammals; RNA Stability; RNA, Antisense; RNA, Double-Stranded
PubMed: 36038571
DOI: 10.1038/s41467-022-32537-0 -
Frontiers in Cellular and Infection... 2014Listeria monocytogenes is a Gram-positive human-pathogen bacterium that served as an experimental model for investigating fundamental processes of adaptive immunity and... (Review)
Review
Listeria monocytogenes is a Gram-positive human-pathogen bacterium that served as an experimental model for investigating fundamental processes of adaptive immunity and virulence. Recent novel technologies allowed the identification of several hundred non-coding RNAs (ncRNAs) in the Listeria genome and provided insight into an unexpected complex transcriptional machinery. In this review, we discuss ncRNAs that are encoded on the opposite strand of the target gene and are therefore termed antisense RNAs (asRNAs). We highlight mechanistic and functional concepts of asRNAs in L. monocytogenes and put these in context of asRNAs in other bacteria. Understanding asRNAs will further broaden our knowledge of RNA-mediated gene regulation and may provide targets for diagnostic and antimicrobial development.
Topics: Gene Expression Regulation, Bacterial; Listeria monocytogenes; RNA, Antisense; RNA, Bacterial
PubMed: 25325017
DOI: 10.3389/fcimb.2014.00135