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Current Opinion in Microbiology Apr 2007Classic antisense RNA research has focused on detailed examination of a few plasmid-encoded systems whilst more recent efforts have focused on chromosomally encoded... (Review)
Review
Classic antisense RNA research has focused on detailed examination of a few plasmid-encoded systems whilst more recent efforts have focused on chromosomally encoded small RNAs. Recent work on newly identified plasmid-encoded antisense RNAs suggest that there is still much to learn from them about the versatility of regulatory RNAs. The alpha-proteobacterial repABC plasmids produce an antisense RNA that regulates the replication initiator independently of the partition proteins encoded in the same operon. The Staphylococcus aureus plasmid pSK41 produces an antisense RNA that regulates the replication initiator protein by a translational attenuation mechanism. Enterococcus faecalis pheromone-responsive plasmids produce plasmid-specific variants of an antisense RNA that regulates conjugation structural genes by a transcriptional attenuation mechanism. E. faecalis plasmid pAD1 encodes an antisense RNA-regulated addiction module that combines features of classic plasmid-encoded and trans-regulated chromosomally encoded antisense systems. Studies on these systems will expand our understanding of the repertoire of small RNA regulators.
Topics: Bacteria; Conjugation, Genetic; Gram-Positive Bacteria; Plasmids; RNA, Antisense; RNA, Bacterial; Staphylococcus aureus
PubMed: 17376732
DOI: 10.1016/j.mib.2007.03.002 -
Neurochemistry International Sep 1997The use of synthetic antisense oligonucleotides as specific inhibitors of gene expression exploits the susceptibility of mRNA to functional blockade at several levels,... (Review)
Review
The use of synthetic antisense oligonucleotides as specific inhibitors of gene expression exploits the susceptibility of mRNA to functional blockade at several levels, including mRNA processing, transport, translation and degradation. It is becoming increasingly apparent that the actions of these synthetic oligomers are analogous to those of endogenous RNA molecules involved in the regulation of gene expression in both prokaryotes and eukaryotes. A growing number of eukaryotic genes are now thought to be regulated at least in part by natural antisense RNA transcribed from the presumptive non-coding DNA strand. This possibility is supported by the presence of a complex system of double-stranded (ds) RNA-specific proteins and dsRNA-induced signal transduction pathways in eukaryotic cells. The presence of functional open reading frames in a number of recognized natural antisense RNA transcripts indicates that, in addition to regulating gene function at the RNA level, the antisense strand of many genes may code for as yet unidentified proteins. In the present study we review the current literature on the role(s) played by natural antisense RNA in eukaryotic cells, with an emphasis on genes for which clear evidence of regulation, or potential regulation by natural antisense RNA is available.
Topics: Animals; Conserved Sequence; Gene Expression Regulation; Genes, Homeobox; Growth Substances; Humans; Proto-Oncogenes; RNA, Antisense; RNA, Messenger; Transcription, Genetic
PubMed: 9246680
DOI: 10.1016/s0197-0186(96)00108-8 -
Nature Reviews. Microbiology Feb 2013In recent years, non-coding RNAs have emerged as key regulators of gene expression. Among these RNAs, the antisense RNAs (asRNAs) are particularly abundant, but in most... (Review)
Review
In recent years, non-coding RNAs have emerged as key regulators of gene expression. Among these RNAs, the antisense RNAs (asRNAs) are particularly abundant, but in most cases the function and mechanism of action for a particular asRNA remains elusive. Here, we highlight a recently discovered paradigm termed the excludon, which defines a genomic locus encoding an unusually long asRNA that spans divergent genes or operons with related or opposing functions. Because these asRNAs can inhibit the expression of one operon while functioning as an mRNA for the adjacent operon, they act as fine-tuning regulatory switches in bacteria.
Topics: Bacteria; Bacterial Proteins; Gene Expression Regulation, Bacterial; Genome, Bacterial; Operon; Protein Biosynthesis; RNA, Antisense; RNA, Bacterial; RNA, Messenger; Trans-Activators; Transcriptome
PubMed: 23268228
DOI: 10.1038/nrmicro2934 -
Nucleic Acids Research Jul 2011Restriction-modification systems consist of a modification enzyme that methylates a specific DNA sequence and a restriction endonuclease that cleaves DNA lacking this...
Restriction-modification systems consist of a modification enzyme that methylates a specific DNA sequence and a restriction endonuclease that cleaves DNA lacking this epigenetic signature. Their gene expression should be finely regulated because their potential to attack the host bacterial genome needs to be controlled. In the EcoRI system, where the restriction gene is located upstream of the modification gene in the same orientation, we previously identified intragenic reverse promoters affecting gene expression. In the present work, we identified a small (88 nt) antisense RNA (Rna0) transcribed from a reverse promoter (P(REV0)) at the 3' end of the restriction gene. Its antisense transcription, as measured by transcriptional gene fusion, appeared to be terminated by the P(M1,M2) promoter. P(M1,M2) promoter-initiated transcription, in turn, appeared to be inhibited by P(REV0). Mutational inactivation of P(REV0) increased expression of the restriction gene. The biological significance of this antisense transcription is 2-fold. First, a mutation in P(REV0) increased restriction of incoming DNA. Second, the presence of the antisense RNA gene (ecoRIA) in trans alleviated cell killing after loss of the EcoRI plasmid (post-segregational killing). Taken together, these results strongly suggested the involvement of an antisense RNA in the biological regulation of this restriction-modification system.
Topics: Deoxyribonuclease EcoRI; Gene Expression Regulation, Bacterial; Mutation; Promoter Regions, Genetic; RNA, Antisense; Site-Specific DNA-Methyltransferase (Adenine-Specific); Transcription, Genetic
PubMed: 21459843
DOI: 10.1093/nar/gkr166 -
Plant Physiology Sep 2017Our previous study identified approximately 6,000 abiotic stress-responsive noncoding transcripts existing on the antisense strand of protein-coding genes and implied...
Our previous study identified approximately 6,000 abiotic stress-responsive noncoding transcripts existing on the antisense strand of protein-coding genes and implied that a type of antisense RNA was synthesized from a sense RNA template by (). Expression analyses revealed that the expression of novel abiotic stress-induced antisense RNA on 1,136 gene loci was reduced in the mutants. RNase protection indicated that the antisense RNA and other RDR1/2/6-dependent antisense RNAs are involved in the formation of dsRNA. The accumulation of stress-inducible antisense RNA was decreased and increased in and , respectively, but not changed in , and RNA-seq analyses revealed that the majority of the RDR1/2/6-dependent antisense RNA loci did not overlap with RDR1/2/6-dependent 20-30 nt RNA loci. Additionally, mutants decreased the degradation rate of the sense RNA and exhibited arrested root growth during the recovery stage following a drought stress, whereas mutants did not. Collectively, these results indicate that RDRs have stress-inducible antisense RNA synthesis activity and a novel biological function that is different from the known endogenous small RNA pathways from protein-coding genes. These data reveal a novel mechanism of RNA regulation during abiotic stress response that involves complex RNA degradation pathways.
Topics: Arabidopsis; Genetic Loci; Mutation; Oligonucleotide Array Sequence Analysis; Plant Proteins; RNA, Antisense; RNA-Dependent RNA Polymerase; Stress, Psychological; Transcriptome
PubMed: 28710133
DOI: 10.1104/pp.17.00787 -
Structural Diversity of Sense and Antisense RNA Hexanucleotide Repeats Associated with ALS and FTLD.Molecules (Basel, Switzerland) Jan 2020The hexanucleotide expansion GGGGCC located in gene represents the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar dementia...
The hexanucleotide expansion GGGGCC located in gene represents the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar dementia (FTLD). Since the discovery one of the non-exclusive mechanisms of expanded hexanucleotide GC repeats involved in ALS and FTLD is RNA toxicity, which involves accumulation of pathological sense and antisense RNA transcripts. Formed RNA foci sequester RNA-binding proteins, causing their mislocalization and, thus, diminishing their biological function. Therefore, structures adopted by pathological RNA transcripts could have a key role in pathogenesis of ALS and FTLD. Utilizing NMR spectroscopy and complementary methods, we examined structures adopted by both guanine-rich sense and cytosine-rich antisense RNA oligonucleotides with four hexanucleotide repeats. While both oligonucleotides tend to form dimers and hairpins, the equilibrium of these structures differs with antisense oligonucleotide being more sensitive to changes in pH and sense oligonucleotide to temperature. In the presence of K ions, guanine-rich sense RNA oligonucleotide also adopts secondary structures called G-quadruplexes. Here, we also observed, for the first time, that antisense RNA oligonucleotide forms i-motifs under specific conditions. Moreover, simultaneous presence of sense and antisense RNA oligonucleotides promotes formation of heterodimer. Studied structural diversity of sense and antisense RNA transcripts not only further depicts the complex nature of neurodegenerative diseases but also reveals potential targets for drug design in treatment of ALS and FTLD.
Topics: Amyotrophic Lateral Sclerosis; Base Pairing; C9orf72 Protein; Disease Susceptibility; Frontotemporal Dementia; Humans; Hydrogen-Ion Concentration; Magnetic Resonance Spectroscopy; Nucleic Acid Conformation; Oligonucleotides; Oligonucleotides, Antisense; RNA, Antisense; Repetitive Sequences, Nucleic Acid; Spectrum Analysis; Structure-Activity Relationship; Temperature
PubMed: 31991801
DOI: 10.3390/molecules25030525 -
Trends in Biochemical Sciences Feb 2004In recent years, natural antisense transcripts (NATs) have been implicated in many aspects of eukaryotic gene expression including genomic imprinting, RNA interference,... (Review)
Review
In recent years, natural antisense transcripts (NATs) have been implicated in many aspects of eukaryotic gene expression including genomic imprinting, RNA interference, translational regulation, alternative splicing, X-inactivation and RNA editing. Moreover, there is growing evidence to suggest that antisense transcription might have a key role in a range of human diseases. Consequently, there have been several recent attempts to identify novel NATs. To date, approximately 2500 mammalian NATs have been found, indicating that antisense transcription might be a common mechanism of regulating gene expression in human cells. There are increasingly diverse ways in which antisense transcription can regulate gene expression and evidence for the involvement of NATs in human disease is emerging. A range of bioinformatic resources could be used to assist future antisense research.
Topics: Alternative Splicing; Animals; Dosage Compensation, Genetic; Gene Expression Regulation; Genomic Imprinting; Humans; Internet; Models, Biological; Protein Biosynthesis; RNA Editing; RNA Interference; RNA, Antisense; Transcription, Genetic
PubMed: 15102435
DOI: 10.1016/j.tibs.2003.12.002 -
Advances in Experimental Medicine and... 2021Current efforts to design supercharged protein assemblies have opened the door for the creation of substrates that could be used for drug delivery and as substrates for...
Current efforts to design supercharged protein assemblies have opened the door for the creation of substrates that could be used for drug delivery and as substrates for antiviral delivery mechanisms. We explore the potential for antiviral delivery with antisense RNAs that bind their phosphate backbone to the charge of an engineered protein oligomer, providing structural integrity to the RNA strand and adding possible steric effects to prevent reaction with unintended targets.
Topics: Proteins; RNA, Antisense
PubMed: 35023089
DOI: 10.1007/978-3-030-78787-5_7 -
Journal of Bacteriology Oct 2004The par stability determinant, encoded by the Enterococcus faecalis plasmid pAD1, is the only antisense RNA regulated postsegregational killing system identified in...
The par stability determinant, encoded by the Enterococcus faecalis plasmid pAD1, is the only antisense RNA regulated postsegregational killing system identified in gram-positive bacteria. Because of the unique organization of the par locus, the par antisense RNA, RNA II, binds to its target, RNA I, at relatively small, interspersed regions of complementarity. The results of this study suggest that, rather than targeting the antisense bound message for rapid degradation, as occurs in most other antisense RNA regulated systems, RNA I and RNA II form a relatively stable, presumably translationally inactive complex. The stability of the RNA I-RNA II complex would allow RNA I to persist in an untranslated state unless or until the encoding plasmid was lost. After plasmid loss, RNA II would be removed from the complex, allowing translational activation of RNA I. The mechanism of RNA I activation in vivo is unknown, but in vitro dissociation experiments suggest that active removal of RNA II, for example by a cellular RNase, may be required.
Topics: Amino Acid Sequence; Enterococcus faecalis; Molecular Sequence Data; Plasmids; RNA; RNA, Antisense; RNA, Bacterial
PubMed: 15375120
DOI: 10.1128/JB.186.19.6400-6408.2004 -
Microbiology Spectrum Jul 2018Although bacterial genomes are usually densely protein-coding, genome-wide mapping approaches of transcriptional start sites revealed that a significant fraction of the... (Review)
Review
Although bacterial genomes are usually densely protein-coding, genome-wide mapping approaches of transcriptional start sites revealed that a significant fraction of the identified promoters drive the transcription of noncoding RNAs. These can be -acting RNAs, mainly originating from intergenic regions and, in many studied examples, possessing regulatory functions. However, a significant fraction of these noncoding RNAs consist of natural antisense transcripts (asRNAs), which overlap other transcriptional units. Naturally occurring asRNAs were first observed to play a role in bacterial plasmid replication and in bacteriophage λ more than 30 years ago. Today's view is that asRNAs abound in all three domains of life. There are several examples of asRNAs in bacteria with clearly defined functions. Nevertheless, many asRNAs appear to result from pervasive initiation of transcription, and some data point toward global functions of such widespread transcriptional activity, explaining why the search for a specific regulatory role is sometimes futile. In this review, we give an overview about the occurrence of antisense transcription in bacteria, highlight particular examples of functionally characterized asRNAs, and discuss recent evidence pointing at global relevance in RNA processing and transcription-coupled DNA repair.
Topics: Bacteria; Bacterial Proteins; DNA Repair; Evolution, Molecular; Gene Expression Regulation, Bacterial; Genome, Bacterial; Plasmids; RNA, Antisense; RNA, Bacterial; RNA, Untranslated; Transcription, Genetic
PubMed: 30003872
DOI: 10.1128/microbiolspec.RWR-0029-2018