Does everything now make (anti)sense?

2006 ◽  
Vol 34 (6) ◽  
pp. 1148-1150 ◽  
Author(s):  
J.A. Timmons ◽  
L. Good
Keyword(s):  
Gene Expression ◽  
Antisense Rna ◽  
Functional Annotation ◽  
Rna World ◽  
Antisense Transcription ◽  
Functional Importance ◽  
Protein Coding ◽  
Species Diversification ◽  
Mammalian Genomes ◽  
Powerful Mechanism

The data generated by the FANTOM (Functional Annotation of Mouse) consortium, Compugen and Affymetrix have collectively provided evidence that most of the mammalian genomes are actively transcribed. The emergence of an antisense RNA world brings new practical complexities to the study and detection of gene expression. However, we also need to address the fundamental questions regarding the functional importance of these molecules. In this brief paper, we focus on non-coding natural antisense transcription, as it appears to be a potentially powerful mechanism for extending the complexity of the protein coding genome, which is currently unable to explain inter-species diversification.

scholarly journals The Signal and the Noise: Characteristics of Antisense RNA in Complex Microbial Communities

mSystems ◽  
2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Thomas Yssing Michaelsen ◽  
Jakob Brandt ◽  
Caitlin Margaret Singleton ◽  
Rasmus Hansen Kirkegaard ◽  
Johanna Wiesinger ◽  
...  
Keyword(s):  
Gene Expression ◽  
Microbial Communities ◽  
Antisense Rna ◽  
Antisense Transcription ◽  
Individual Species ◽  
Data Sets ◽  
Antisense Expression ◽  
Noise Characteristics ◽  
Starting Point ◽  
Insight Into

ABSTRACT High-throughput sequencing has allowed unprecedented insight into the composition and function of complex microbial communities. With metatranscriptomics, it is possible to interrogate the transcriptomes of multiple organisms simultaneously to get an overview of the gene expression of the entire community. Studies have successfully used metatranscriptomics to identify and describe relationships between gene expression levels and community characteristics. However, metatranscriptomic data sets contain a rich suite of additional information that is just beginning to be explored. Here, we focus on antisense expression in metatranscriptomics, discuss the different computational strategies for handling it, and highlight the strengths but also potentially detrimental effects on downstream analysis and interpretation. We also analyzed the antisense transcriptomes of multiple genomes and metagenome-assembled genomes (MAGs) from five different data sets and found high variability in the levels of antisense transcription for individual species, which were consistent across samples. Importantly, we challenged the conceptual framework that antisense transcription is primarily the product of transcriptional noise and found mixed support, suggesting that the total observed antisense RNA in complex communities arises from the combined effect of unknown biological and technical factors. Antisense transcription can be highly informative, including technical details about data quality and novel insight into the biology of complex microbial communities. IMPORTANCE This study systematically evaluated the global patterns of microbial antisense expression across various environments and provides a bird’s-eye view of general patterns observed across data sets, which can provide guidelines in our understanding of antisense expression as well as interpretation of metatranscriptomic data in general. This analysis highlights that in some environments, antisense expression from microbial communities can dominate over regular gene expression. We explored some potential drivers of antisense transcription, but more importantly, this study serves as a starting point, highlighting topics for future research and providing guidelines to include antisense expression in generic bioinformatic pipelines for metatranscriptomic data.

scholarly journals Regulation of antisense RNA expression during cardiac MHC gene switching in response to pressure overload

2006 ◽  
Vol 290 (6) ◽  
pp. H2351-H2361 ◽  
Author(s):  
F. Haddad ◽  
A. X. Qin ◽  
P. W. Bodell ◽  
L. Y. Zhang ◽  
H. Guo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Left Ventricle ◽  
Mrna Expression ◽  
Antisense Rna ◽  
Pressure Overload ◽  
Antisense Transcription ◽  
Regulatory Sequences ◽  
Rna Regulation ◽  
Regulation Scheme ◽  
Antisense Regulation

Hypertension has been shown to cause cardiac hypertrophy and a shift in myosin heavy chain (MHC) gene expression from the faster α- to slower β-MHC isoform. The expression of the β- and α-MHC pre-mRNAs, mRNAs, as well as the newly discovered antisense β-RNA were analyzed in three regions of the normal control (NC) and 12-day pressure-overloaded (AbCon) hearts: the left ventricle apex, left ventricle base, and the septum. The RNA analyses in the AbCon heart targeted both the 5′ and the 3′ ends of each RNA molecule. β-MHC mRNA expression significantly increased relative to control in all three regions, regardless of the target site (5′ or 3′ end). In contrast, β-MHC pre-mRNA expression in the AbCon heart depended on the site of the measurement (5′ vs. 3′ end). For example, whereas the pre-mRNA did not change when targeted at the 3′ end (last intron), it increased significantly in the AbCon heart when measurement targeted the 5′ end (2nd intron) of the 25-kb molecule. Analyses of the antisense β-RNA revealed that its expression in the AbCon heart was significantly decreased relative to control regardless of its measurement site. A negative correlation was observed between the β-mRNA expression and the antisense β-RNA ( P < 0.05), suggesting an inhibitory role of antisense RNA on the sense β-MHC gene expression. In contrast, a positive correlation was observed between the antisense β-RNA and the α-MHC pre-mRNA ( P < 0.05). This latter observation along with the α-MHC gene position relative to that of the β-antisense suggest that the α-MHC sense and β-antisense transcription are coregulated likely via common intergenic regulatory sequences. Our results suggest that the increased β-MHC expression in the AbCon heart not only is the result of increased β-MHC transcription but also involves an antisense β-RNA regulation scheme. Although the exact mechanism concerning antisense regulation is not clear, it could involve modulation of both transcriptional activity of the β-MHC gene and posttranscriptional processing.

scholarly journals A novel pH-regulated, unusual 603 bp overlapping protein coding gene pop is encoded antisense to ompA in Escherichia coli O157:H7 (EHEC)

2019 ◽  
Author(s):  
Barbara Zehentner ◽  
Zachary Ardern ◽  
Michaela Kreitmeier ◽  
Siegfried Scherer ◽  
Klaus Neuhaus
Keyword(s):  
Antisense Rna ◽  
Prokaryotic Genome ◽  
Antisense Transcription ◽  
Ribosome Profiling ◽  
Escherichia Coli O157 ◽  
Overlapping Genes ◽  
Western Blots ◽  
Protein Coding ◽  
Reading Frame ◽  
Growth Experiments

AbstractAntisense transcription is well known in bacteria. However, translation of antisense RNAs is typically not considered, as the implied overlapping coding at a DNA locus is assumed to be highly improbable. Therefore, such overlapping genes are systematically excluded in prokaryotic genome annotation. Here we report an exceptional 603 bp long open reading frame completely embedded in antisense to the gene of the outer membrane protein ompA. Ribosomal profiling revealed translation of the mRNA and the protein was detected in Western blots. A σ70 promoter, transcription start site, Shine-Dalgarno motif and rho-independent terminator were experimentally validated. A pH-dependent phenotype conferred by the protein was shown in competitive overexpression growth experiments of a translationally arrested mutant versus wild type. We designate this novel gene pop (pH-regulated overlapping protein-coding gene). Increasing evidence based on ribosome-profiling indicates translation of antisense RNA, suggesting that more overlapping genes of unknown function may exist in bacteria.

scholarly journals The Paf1 complex broadly impacts the transcriptome ofSaccharomyces cerevisiae

2019 ◽  
Author(s):  
Mitchell A. Ellison ◽  
Alex R. Lederer ◽  
Marcie H. Warner ◽  
Travis Mavrich ◽  
Elizabeth A. Raupach ◽  
...  
Keyword(s):  
Gene Expression ◽  
De Novo ◽  
Differential Expression Analysis ◽  
Chromatin Modification ◽  
Antisense Transcription ◽  
Yeast Genome ◽  
Mrna Levels ◽  
Nascent Transcript ◽  
Protein Coding ◽  
Multiple Loci

ABSTRACTThe Polymerase Associated Factor 1 complex (Paf1C) is a multifunctional regulator of eukaryotic gene expression important for the coordination of transcription with chromatin modification and post-transcriptional processes. In this study, we investigated the extent to which the functions of Paf1C combine to regulate theSaccharomyces cerevisiaetranscriptome. While previous studies focused on the roles of Paf1C in controlling mRNA levels, here we took advantage of a genetic background that enriches for unstable transcripts and demonstrate that deletion ofPAF1affects all classes of Pol II transcripts including multiple classes of noncoding RNAs. By conducting ade novodifferential expression analysis independent of gene annotations, we found that Paf1 positively and negatively regulates antisense transcription at multiple loci. Comparisons with nascent transcript data revealed that many, but not all, changes in RNA levels detected by our analysis are due to changes in transcription instead of post-transcriptional events. To investigate the mechanisms by which Paf1 regulates protein-coding genes, we focused on genes involved in iron and phosphate homeostasis, which were differentially affected byPAF1deletion. Our results indicate that Paf1 stimulates phosphate gene expression through a mechanism that is independent of any individual Paf1C-dependent histone modification. In contrast, the inhibition of iron gene expression by Paf1 correlates with a defect in H3 K36 tri-methylation. Finally, we showed that one iron regulon gene,FET4, is coordinately controlled by Paf1 and transcription of upstream noncoding DNA. Together these data identify roles for Paf1C in controlling both coding and noncoding regions of the yeast genome.

scholarly journals Promoter switching in response to changing environment and elevated expression of protein-coding genes overlapping at their 5’ ends

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Wojciech Rosikiewicz ◽  
Jarosław Sikora ◽  
Tomasz Skrzypczak ◽  
Magdalena R. Kubiak ◽  
Izabela Makałowska
Keyword(s):  
Gene Expression ◽  
Antisense Transcription ◽  
Changing Environment ◽  
Antisense Gene ◽  
Protein Coding ◽  
Normal Tissues ◽  
Regulatory Processes ◽  
Elevated Expression ◽  
A Cell ◽  
Cancerous Cells

AbstractDespite the number of studies focused on sense-antisense transcription, the key question of whether such organization evolved as a regulator of gene expression or if this is only a byproduct of other regulatory processes has not been elucidated to date. In this study, protein-coding sense-antisense gene pairs were analyzed with a particular focus on pairs overlapping at their 5’ ends. Analyses were performed in 73 human transcription start site libraries. The results of our studies showed that the overlap between genes is not a stable feature and depends on which TSSs are utilized in a given cell type. An analysis of gene expression did not confirm that overlap between genes causes downregulation of their expression. This observation contradicts earlier findings. In addition, we showed that the switch from one promoter to another, leading to genes overlap, may occur in response to changing environment of a cell or tissue. We also demonstrated that in transfected and cancerous cells genes overlap is observed more often in comparison with normal tissues. Moreover, utilization of overlapping promoters depends on particular state of a cell and, at least in some groups of genes, is not merely coincidental.

scholarly journals The signal and the noise - characteristics of antisense RNA in complex microbial communities

2019 ◽  
Author(s):  
Thomas Yssing Michaelsen ◽  
Jakob Brandt ◽  
Caitlin Singleton ◽  
Rasmus Hansen Kirkegaard ◽  
Nicola Segata ◽  
...  
Keyword(s):  
Gene Expression ◽  
Microbial Communities ◽  
Antisense Rna ◽  
High Throughput Sequencing ◽  
Antisense Transcription ◽  
Individual Species ◽  
List Type ◽  
Additional Information ◽  
Noise Characteristics ◽  
Insight Into

AbstractHigh-throughput sequencing has allowed unprecedented insight into the composition and function of complex microbial communities. With the onset of metatranscriptomics, it is now possible to interrogate the transcriptome of multiple organisms simultaneously to get an overview of the gene expression of the entire community. Studies have successfully used metatranscriptomics to identify and describe relationships between gene expression levels and community characteristics. However, metatranscriptomic datasets contain a rich suite of additional information which is just beginning to be explored. In this minireview we discuss the different computational strategies for handling antisense expression in metatranscriptomic samples and highlight their potentially detrimental effects on downstream analysis and interpretation. We also surveyed the antisense transcriptome of multiple genomes and metagenome-assembled genomes (MAGs) from five different datasets and found high variability in the level of antisense transcription for individual species which were consistent across samples. Importantly, we tested the hypothesis that antisense transcription is primarily the product of transcriptional noise and found mixed support, suggesting that the total observed antisense RNA in complex communities arises from a compounded effect of both random, biological and technical factors. Antisense transcription can provide a rich set of information, from technical details about data quality to novel insight into the biology of complex microbial communities.Key pointsSeveral fundamentally different approaches are used to handle antisense RNAPrevalence of antisense RNA is highly variable between communities, genomes, and genes.Antisense RNA is likely an opaque mixture of technical, biological and random effects

scholarly journals Neighborhood regulation by lncRNA promoters, transcription, and splicing

2016 ◽  
Author(s):  
Jesse M. Engreitz ◽  
Jenna E. Haines ◽  
Glen Munson ◽  
Jenny Chen ◽  
Elizabeth M. Perez ◽  
...  
Keyword(s):  
Gene Expression ◽  
Rna Splicing ◽  
Regulation Of Gene Expression ◽  
Noncoding Rnas ◽  
Gene Promoters ◽  
Neighboring Gene ◽  
Protein Coding ◽  
Local Regulation ◽  
Genetic Manipulations ◽  
Mammalian Genomes

AbstractMammalian genomes are pervasively transcribed to produce thousands of spliced long noncoding RNAs (lncRNAs), whose functions remain poorly understood. Because recent evidence has implicated several specific lncRNA loci in the local regulation of gene expression, we sought to determine whether such local regulation is a property of many lncRNA loci. We used genetic manipulations to dissect 12 genomic loci that produce lncRNAs and found that 5 of these loci influence the expression of a neighboring gene in cis. Surprisingly, however, none of these effects required the specific lncRNA transcripts themselves and instead involved general processes associated with their production, including enhancer-like activity of gene promoters, the process of transcription, and the splicing of the transcript. Interestingly, such effects are not limited to lncRNA loci: we found similar effects on local gene expression at 4 of 6 protein-coding loci. These results demonstrate that ‘crosstalk’ among neighboring genes is a prevalent phenomenon that can involve multiple mechanisms and cis regulatory signals, including a novel role for RNA splicing. These mechanisms may explain the function and evolution of some genomic loci that produce lncRNAs.

scholarly journals Alternative splicing during mammalian organ development

2021 ◽  
Author(s):  
Pavel V. Mazin ◽  
Philipp Khaitovich ◽  
Margarida Cardoso-Moreira ◽  
Henrik Kaessmann
Keyword(s):  
Gene Expression ◽  
Alternative Splicing ◽  
Regulatory Networks ◽  
Organ Development ◽  
Functional Diversification ◽  
Mammalian Genomes ◽  
Species Comparisons ◽  
Time Specific ◽  
The Brain ◽  
Gene Expression Levels

AbstractAlternative splicing (AS) is pervasive in mammalian genomes, yet cross-species comparisons have been largely restricted to adult tissues and the functionality of most AS events remains unclear. We assessed AS patterns across pre- and postnatal development of seven organs in six mammals and a bird. Our analyses revealed that developmentally dynamic AS events, which are especially prevalent in the brain, are substantially more conserved than nondynamic ones. Cassette exons with increasing inclusion frequencies during development show the strongest signals of conserved and regulated AS. Newly emerged cassette exons are typically incorporated late in testis development, but those retained during evolution are predominantly brain specific. Our work suggests that an intricate interplay of programs controlling gene expression levels and AS is fundamental to organ development, especially for the brain and heart. In these regulatory networks, AS affords substantial functional diversification of genes through the generation of tissue- and time-specific isoforms from broadly expressed genes.

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