scholarly journals HIV-1 Natural Antisense Transcription and Its Role in Viral Persistence

Viruses ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 795
Author(s):  
Rui Li ◽  
Rachel Sklutuis ◽  
Jennifer L. Groebner ◽  
Fabio Romerio
Keyword(s):  
Current Knowledge ◽  
Antisense Transcription ◽  
Future Research ◽  
Antisense Transcripts ◽  
Protein Coding ◽  
Rna Molecules ◽  
Immunodeficiency Virus ◽  
Opposite Strand ◽  
Cognate Protein ◽  
Hiv 1

Natural antisense transcripts (NATs) represent a class of RNA molecules that are transcribed from the opposite strand of a protein-coding gene, and that have the ability to regulate the expression of their cognate protein-coding gene via multiple mechanisms. NATs have been described in many prokaryotic and eukaryotic systems, as well as in the viruses that infect them. The human immunodeficiency virus (HIV-1) is no exception, and produces one or more NAT from a promoter within the 3’ long terminal repeat. HIV-1 antisense transcripts have been the focus of several studies spanning over 30 years. However, a complete appreciation of the role that these transcripts play in the virus lifecycle is still lacking. In this review, we cover the current knowledge about HIV-1 NATs, discuss some of the questions that are still open and identify possible areas of future research.

scholarly journals The Therapeutic Potential of Ribozymes

Blood ◽  
1998 ◽  
Vol 91 (2) ◽  
pp. 371-382 ◽  
Author(s):  
Helen A. James ◽  
Ian Gibson
Keyword(s):  
Therapeutic Potential ◽  
New Developments ◽  
Rna Molecules ◽  
Viral Genomes ◽  
Chromosome Translocations ◽  
Immunodeficiency Virus ◽  
Deleterious Gene ◽  
Target Rna ◽  
Hiv 1

Ribozymes are catalytic RNA molecules that recognize their target RNA in a highly sequence-specific manner. They can therefore be used to inhibit deleterious gene expression (by cleavage of the target mRNA) or even repair mutant cellular RNAs. Targets such as the mRNAs of oncogenes (resulting from base mutations or chromosome translocations, eg, ras or bcr-abl) and viral genomes and transcripts (human immunodeficiency virus–type 1 [HIV-1]) are ideal targets for such sequence-specific agents. The aim of this review is therefore to introduce the different classes of ribozymes, highlighting some of the chemistry of the reactions they catalyze, to address the specific inhibition of genes by ribozymes, the problems yet to be resolved, and how new developments in the field give hope to the future for ribozymes in the therapeutic field.

scholarly journals Genomic determinants for initiation and length of natural antisense transcripts in Entamoeba histolytica

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Damien Mornico ◽  
Chung-Chau Hon ◽  
Mikael Koutero ◽  
Christian Weber ◽  
Jean-Yves Coppee ◽  
...  
Keyword(s):  
Gene Expression ◽  
Entamoeba Histolytica ◽  
Regulatory System ◽  
Antisense Transcripts ◽  
Natural Antisense Transcripts ◽  
Protein Coding ◽  
Transcription Start Sites ◽  
Spurious Transcription ◽  
Intergenic Regions ◽  
Opposite Strand

AbstractNatural antisense transcripts (NAT) have been reported in prokaryotes and eukaryotes. While the functions of most reported NATs remain unknown, their potentials in regulating the transcription of their counterparts have been speculated. Entamoeba histolytica, which is a unicellular eukaryotic parasite, has a compact protein-coding genome with very short intronic and intergenic regions. The regulatory mechanisms of gene expression in this compact genome are under-described. In this study, by genome-wide mapping of RNA-Seq data in the genome of E. histolytica, we show that a substantial fraction of its protein-coding genes (28%) has significant transcription on their opposite strand (i.e. NAT). Intriguingly, we found the location of transcription start sites or polyadenylation sites of NAT are determined by the specific motifs encoded on the opposite strand of the gene coding sequences, thereby providing a compact regulatory system for gene transcription. Moreover, we demonstrated that NATs are globally up-regulated under various environmental conditions including temperature stress and pathogenicity. While NATs do not appear to be consequences of spurious transcription, they may play a role in regulating gene expression in E. histolytica, a hypothesis which needs to be tested.

scholarly journals A mikro-RNS-ek szerepe az agyalapimirigy-daganatok tumorbiológiájában

2018 ◽  
Vol 159 (7) ◽  
pp. 252-259 ◽  
Author(s):  
Kinga Németh ◽  
Ottó Darvasi ◽  
Nikolette Szücs ◽  
Sándor Czirják ◽  
Henriett Butz
Keyword(s):  
Pituitary Adenoma ◽  
Posttranscriptional Regulation ◽  
Target Gene ◽  
Target Genes ◽  
Current Knowledge ◽  
Cellular Mechanisms ◽  
Protein Coding ◽  
Rna Molecules ◽  
Mirna Expression Pattern ◽  
Different Types

Abstract: MicroRNAs (miRNAs) are short, single stranded RNA molecules which play regulatory roles through posttranscriptional regulation of their target genes. Based on our current knowledge, more than 30% of the human protein-coding genes are regulated by miRNAs, hence influencing basic cellular mechanisms including cell proliferation, differentiation and cell death. Differential miRNA expression pattern has been detected in many different types of tumors and, recently, several publications have referred to miRNAs as potential therapeutic targets. Through adjustment of miRNA levels by artificial miRNAs administration or miRNA inhibition, we can influence not only one target gene but also complex biological pathways. Pituitary adenoma is the second most frequent intracranial tumor. In spite of this, the molecular mechanism of the pituitary adenoma formation is not yet entirely revealed. Recently, more and more evidences have been found suggesting that miRNAs have an important role in pituitary adenoma pathogenesis. Here, we summarize the recent results related to this role and highlight the therapeutic potentials in pituitary adenomas. Orv Hetil. 2018; 159(7): 252–259.

scholarly journals Amplification of a Complete Simian Immunodeficiency Virus Genome from Fecal RNA of a Wild Chimpanzee

2003 ◽  
Vol 77 (3) ◽  
pp. 2233-2242 ◽  
Author(s):  
Mario L. Santiago ◽  
Frederic Bibollet-Ruche ◽  
Elizabeth Bailes ◽  
Shadrack Kamenya ◽  
Martin N. Muller ◽  
...  
Keyword(s):  
Simian Immunodeficiency Virus ◽  
Pan Troglodytes ◽  
Current Knowledge ◽  
Extended Period ◽  
Amino Acid Sequences ◽  
Primate Species ◽  
Wild Chimpanzee ◽  
West Central ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Current knowledge of the genetic diversity of simian immunodeficiency virus (SIVcpz) infection of wild chimpanzees (Pan troglodytes) is incomplete since few isolates, mostly from captive apes from Cameroon and Gabon, have been characterized; yet this information is critical for understanding the origins of human immunodeficiency virus type 1 (HIV-1) and the circumstances leading to the HIV-1 pandemic. Here, we report the first full-length SIVcpz sequence (TAN1) from a wild chimpanzee (Pan troglodytes schweinfurthii) from Gombe National Park (Tanzania), which was obtained noninvasively by amplification of virion RNA from fecal samples collected under field conditions. Using reverse transcription-PCR and a combination of generic and strain-specific primers, we amplified 13 subgenomic fragments which together spanned the entire TAN1 genome (9,326 bp). Distance and phylogenetic tree analyses identified TAN1 unambiguously as a member of the HIV-1/SIVcpz group of viruses but also revealed an extraordinary degree of divergence from all previously characterized SIVcpz and HIV-1 strains. In Gag, Pol, and Env proteins, TAN1 differed from west-central African SIVcpz and HIV-1 strains on average by 36, 30, and 51% of amino acid sequences, respectively, approaching distance values typically found for SIVs from different primate species. The closest relative was SIVcpzANT, also from a P. t. schweinfurthii ape, which differed by 30, 25, and 44%, respectively, in these same protein sequences but clustered with TAN1 in all major coding regions in a statistically highly significant manner. These data indicate that east African chimpanzees, like those from west-central Africa, are naturally infected by SIVcpz but that their viruses comprise a second, divergent SIVcpz lineage which appears to have evolved in relative isolation for an extended period of time. Our data also demonstrate that noninvasive molecular epidemiological studies of SIVcpz in wild chimpanzees are feasible and that such an approach may prove essential for unraveling the evolutionary history of SIVcpz/HIV-1 as well as that of other pathogens naturally infecting wild primate populations.

scholarly journals LncRNAs in domesticated animals: from dog to livestock species

2021 ◽  
Author(s):  
Sandrine Lagarrigue ◽  
Matthias Lorthiois ◽  
Fabien Degalez ◽  
David Gilot ◽  
Thomas Derrien
Keyword(s):  
Current Knowledge ◽  
Domestic Animals ◽  
Genetic Studies ◽  
Protein Coding ◽  
Domesticated Animals ◽  
Case Examples ◽  
Rna Molecules ◽  
Livestock Species ◽  
Functional Characterisation ◽  
Non Coding Rnas

AbstractAnimal genomes are pervasively transcribed into multiple RNA molecules, of which many will not be translated into proteins. One major component of this transcribed non-coding genome is the long non-coding RNAs (lncRNAs), which are defined as transcripts longer than 200 nucleotides with low coding-potential capabilities. Domestic animals constitute a unique resource for studying the genetic and epigenetic basis of phenotypic variations involving protein-coding and non-coding RNAs, such as lncRNAs. This review presents the current knowledge regarding transcriptome-based catalogues of lncRNAs in major domesticated animals (pets and livestock species), covering a broad phylogenetic scale (from dogs to chicken), and in comparison with human and mouse lncRNA catalogues. Furthermore, we describe different methods to extract known or discover novel lncRNAs and explore comparative genomics approaches to strengthen the annotation of lncRNAs. We then detail different strategies contributing to a better understanding of lncRNA functions, from genetic studies such as GWAS to molecular biology experiments and give some case examples in domestic animals. Finally, we discuss the limitations of current lncRNA annotations and suggest research directions to improve them and their functional characterisation.

scholarly journals Antisense Transcripts and Antisense Protein: A New Perspective on Human Immunodeficiency Virus Type 1

2021 ◽  
Vol 11 ◽  
Author(s):  
Juliette Savoret ◽  
Jean-Michel Mesnard ◽  
Antoine Gross ◽  
Nathalie Chazal
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Protein A ◽  
Antisense Transcripts ◽  
Reading Frame ◽  
Immunodeficiency Virus ◽  
New Perspective ◽  
Hiv 1

It was first predicted in 1988 that there may be an Open Reading Frame (ORF) on the negative strand of the Human Immunodeficiency Virus type 1 (HIV-1) genome that could encode a protein named AntiSense Protein (ASP). In spite of some controversy, reports began to emerge some years later describing the detection of HIV-1 antisense transcripts, the presence of ASP in transfected and infected cells, and the existence of an immune response targeting ASP. Recently, it was established that the asp gene is exclusively conserved within the pandemic group M of HIV-1. In this review, we summarize the latest findings on HIV-1 antisense transcripts and ASP, and we discuss their potential functions in HIV-1 infection together with the role played by antisense transcripts and ASPs in some other viruses. Finally, we suggest pathways raised by the study of antisense transcripts and ASPs that may warrant exploration in the future.

scholarly journals The Therapeutic Potential of Ribozymes

Blood ◽  
1998 ◽  
Vol 91 (2) ◽  
pp. 371-382 ◽  
Author(s):  
Helen A. James ◽  
Ian Gibson
Keyword(s):  
Therapeutic Potential ◽  
New Developments ◽  
Rna Molecules ◽  
Viral Genomes ◽  
Chromosome Translocations ◽  
Immunodeficiency Virus ◽  
Deleterious Gene ◽  
Target Rna ◽  
Hiv 1

Abstract Ribozymes are catalytic RNA molecules that recognize their target RNA in a highly sequence-specific manner. They can therefore be used to inhibit deleterious gene expression (by cleavage of the target mRNA) or even repair mutant cellular RNAs. Targets such as the mRNAs of oncogenes (resulting from base mutations or chromosome translocations, eg, ras or bcr-abl) and viral genomes and transcripts (human immunodeficiency virus–type 1 [HIV-1]) are ideal targets for such sequence-specific agents. The aim of this review is therefore to introduce the different classes of ribozymes, highlighting some of the chemistry of the reactions they catalyze, to address the specific inhibition of genes by ribozymes, the problems yet to be resolved, and how new developments in the field give hope to the future for ribozymes in the therapeutic field.

Quantitative assays based on the use of replicatable hybridization probes.

1989 ◽  
Vol 35 (9) ◽  
pp. 1826-1831 ◽  
Author(s):  
H Lomeli ◽  
S Tyagi ◽  
C G Pritchard ◽  
P M Lizardi ◽  
F R Kramer
Keyword(s):  
Human Immunodeficiency Virus ◽  
Guanidine Thiocyanate ◽  
Probe Sequence ◽  
Rna Molecules ◽  
Mrna Targets ◽  
Hybridization Probes ◽  
Target Capture ◽  
Immunodeficiency Virus ◽  
Hiv 1

Abstract Amplifiable hybridization probes--molecules with a probe sequence embedded within the sequence of a replicatable RNA--will promote the development of sensitive clinical assays. To demonstrate their utility, we prepared a recombinant RNA that contained a 30-nucleotide-long probe complementary to a conserved region of the pol gene in human immunodeficiency virus type 1 (HIV-1) mRNA. Test samples were prepared, each containing a different number of HIV-1 transcripts that served as simulated HIV-1 mRNA targets. Hybridizations were carried out in a solution containing the chaotropic salt, guanidine thiocyanate. Probe-target hybrids were isolated by reversible target capture on paramagnetic particles. The probes were then released from their targets and amplified by incubation with the RNA-directed RNA polymerase, Q beta replicase (EC 2.7.7.48). The replicase copied the probes in an exponential manner: after each round of copying, the number of RNA molecules doubled. The amount of RNA synthesized in each reaction (approximately 50 ng) was sufficient to measure without using radioisotopes. Kinetic analysis of the reactions demonstrated that the number of HIV-1 targets originally present in each sample could be determined by measuring the time it took to synthesize a particular amount of RNA (the longer the synthesis took, the fewer the number of targets originally present). The results suggest that clinical assays involving replicatable hybridization probes will be simple, accurate, sensitive, and automatable.

scholarly journals The Functions and Unique Features of LncRNAs in Cancer Development and Tumorigenesis

2021 ◽  
Vol 22 (2) ◽  
pp. 632
Author(s):  
Kenzui Taniue ◽  
Nobuyoshi Akimitsu
Keyword(s):  
Cancer Biology ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Cancer Development ◽  
Biological Functions ◽  
Protein Coding ◽  
Rna Molecules ◽  
The Past ◽  
Cancer Phenotypes ◽  
Coding Potential

Over the past decades, research on cancer biology has focused on the involvement of protein-coding genes in cancer development. Long noncoding RNAs (lncRNAs), which are transcripts longer than 200 nucleotides that lack protein-coding potential, are an important class of RNA molecules that are involved in a variety of biological functions. Although the functions of a majority of lncRNAs have yet to be clarified, some lncRNAs have been shown to be associated with human diseases such as cancer. LncRNAs have been shown to contribute to many important cancer phenotypes through their interactions with other cellular macromolecules including DNA, protein and RNA. Here we describe the literature regarding the biogenesis and features of lncRNAs. We also present an overview of the current knowledge regarding the roles of lncRNAs in cancer from the view of various aspects of cellular homeostasis, including proliferation, survival, migration and genomic stability. Furthermore, we discuss the methodologies used to identify the function of lncRNAs in cancer development and tumorigenesis. Better understanding of the molecular mechanisms involving lncRNA functions in cancer is critical for the development of diagnostic and therapeutic strategies against tumorigenesis.

scholarly journals Circular and long non-coding RNAs and their role in ophthalmologic diseases

2018 ◽  
Author(s):  
Olga Wawrzyniak ◽  
Żaneta Zarębska ◽  
Katarzyna Rolle ◽  
Anna Gotz-Więckowska
Keyword(s):  
Current Knowledge ◽  
Critical Role ◽  
Circular Rna ◽  
Age Related Macular Degeneration ◽  
Circular Rnas ◽  
Protein Coding ◽  
Rna Molecules ◽  
Age Related ◽  
Non Coding Rnas ◽  
Transcriptional Gene Regulation

Long non-coding RNAs are >200-nucleotide-long RNA molecules which lack or have limited protein-coding potential. They can regulate protein formation through several different mechanisms. Similarly, circular RNAs are reported to play a critical role in post-transcriptional gene regulation. Changes in the expression pattern of these molecules are known to underlie various diseases, including cancer, cardiovascular, neurological and immunological disorders (Rinn & Chang, 2012; Sun & Kraus, 2015). Recent studies suggest that they are differentially expressed both in healthy ocular tissues as well as in eye pathologies, such as neovascularization, proliferative vitreoretinopathy, glaucoma, cataract, ocular malignancy or even strabismus (Li et al., 2016). Aetiology of ocular diseases is multifactorial and combines genetic and environmental factors, including epigenetic and non-coding RNAs. In addition, disorders like diabetic retinopathy or age-related macular degeneration lack biomarkers for early detection as well as effective treatment methods that would allow controlling the disease progression at its early stages. The newly discovered non-coding RNAs seem to be the ideal candidates for novel molecular markers and therapeutic strategies. In this review, we summarized the current knowledge about gene expression regulators – long non-coding and circular RNA molecules in eye diseases.

Sign in / Sign up

Export Citation Format

Share Document