scholarly journals Evolutionary Perspective and Expression Analysis of Intronless Genes Highlight the Conservation of Their Regulatory Role

2021 ◽  
Vol 12 ◽  
Author(s):  
Katia Aviña-Padilla ◽  
José Antonio Ramírez-Rafael ◽  
Gabriel Emilio Herrera-Oropeza ◽  
Vijaykumar Yogesh Muley ◽  
Dulce I. Valdivia ◽  
...  
Keyword(s):  
Rna Splicing ◽  
Developmental Disorders ◽  
Functional Divergence ◽  
Wnt Signaling Pathway ◽  
Control Of Gene Expression ◽  
Embryonic Mouse ◽  
Precise Control ◽  
Regulatory Processes ◽  
Intronless Genes ◽  
Eukaryotic Genes

The structure of eukaryotic genes is generally a combination of exons interrupted by intragenic non-coding DNA regions (introns) removed by RNA splicing to generate the mature mRNA. A fraction of genes, however, comprise a single coding exon with introns in their untranslated regions or are intronless genes (IGs), lacking introns entirely. The latter code for essential proteins involved in development, growth, and cell proliferation and their expression has been proposed to be highly specialized for neuro-specific functions and linked to cancer, neuropathies, and developmental disorders. The abundant presence of introns in eukaryotic genomes is pivotal for the precise control of gene expression. Notwithstanding, IGs exempting splicing events entail a higher transcriptional fidelity, making them even more valuable for regulatory roles. This work aimed to infer the functional role and evolutionary history of IGs centered on the mouse genome. IGs consist of a subgroup of genes with one exon including coding genes, non-coding genes, and pseudogenes, which conform approximately 6% of a total of 21,527 genes. To understand their prevalence, biological relevance, and evolution, we identified and studied 1,116 IG functional proteins validating their differential expression in transcriptomic data of embryonic mouse telencephalon. Our results showed that overall expression levels of IGs are lower than those of MEGs. However, strongly up-regulated IGs include transcription factors (TFs) such as the class 3 of POU (HMG Box), Neurog1, Olig1, and BHLHe22, BHLHe23, among other essential genes including the β-cluster of protocadherins. Most striking was the finding that IG-encoded BHLH TFs fit the criteria to be classified as microproteins. Finally, predicted protein orthologs in other six genomes confirmed high conservation of IGs associated with regulating neural processes and with chromatin organization and epigenetic regulation in Vertebrata. Moreover, this study highlights that IGs are essential modulators of regulatory processes, such as the Wnt signaling pathway and biological processes as pivotal as sensory organ developing at a transcriptional and post-translational level. Overall, our results suggest that IG proteins have specialized, prevalent, and unique biological roles and that functional divergence between IGs and MEGs is likely to be the result of specific evolutionary constraints.

scholarly journals Evolutionary Perspective and Expression Analysis of Intronless Genes Highlight the Conservation on Their Regulatory Role

2021 ◽  
Author(s):  
Katia Aviña-Padilla ◽  
José Antonio Ramírez-Rafael ◽  
Gabriel Emilio Herrera-Oropeza ◽  
Vijaykumar Muley ◽  
Dulce I. Valdivia ◽  
...  
Keyword(s):  
Gene Expression ◽  
Rna Splicing ◽  
Developmental Disorders ◽  
Functional Divergence ◽  
Wnt Signaling Pathway ◽  
Early Embryo ◽  
Control Of Gene Expression ◽  
Precise Control ◽  
Intronless Genes ◽  
Eukaryotic Genes

AbstractEukaryotic gene structure is a combination of exons generally interrupted by intragenic non-coding DNA regions termed introns removed by RNA splicing to generate the mature mRNA. Thus, eukaryotic genes can be either single exon genes (SEGs) or multiple exon genes (MEGs). Among SEGs, intronless genes (IGs) are a subgroup that additionally lacks introns at their UTRs, and code for proteins essentially involved in development, growth, and cell proliferation. Gene expression of IGs has been proposed to be highly specialized for neuro-specific functions and linked to cancer, neuropathies, and developmental disorders. The abundant presence of introns in eukaryotic genomes is pivotal for the precise control of gene expression. Notwithstanding, IGs exempting splicing events entail a higher transcriptional fidelity, making them even more valuable for regulatory roles. This work aimed to infer the functional role and evolutionary history of IGs using the mouse genome. Intronless protein-coding genes consist of a subgroup of ~6 % of a total of 21,527 genes with one exon. To understand the prevalence, biological relevance, and evolution, we identified and studied their 1,116 functional proteins. We validated differential expression in transcriptomics data of early embryo stages using mouse telencephalon tissue. Our results showed that expression levels of IGs are lower compared to MEGs. However, strongly upregulated IGs include transcription factors (TFs) such as the class 3 of POU (HMG Box), Neurog1, Olig1, and BHLHe22, BHLHe23, among other essential genes including the beta cluster of protocadherins. Most striking was the finding that IG-encoded BHLH TFs qualify the criteria to be referred to as microprotein candidates. Finally, predicted protein orthologs in other six genomes confirmed a high conservancy of IGs associated with regulating neurobiological processes and with chromatin organization and epigenetic regulation in Vertebrata. Moreover, this study highlights that IGs are essential modulators of regulatory processes, as Wnt signaling pathway and biological processes as pivotal as sensory organs developing at a transcriptional and post-translational level. Overall, our results suggest that IG proteins have specialized, prevalent, and unique biological roles and that functional divergence between IGs and MEGs is likely to be the result of specific evolutionary constraints.

scholarly journals Intron and Its Splicing Mechanism and Their Connection with Human Disease

2016 ◽  
Vol 15 (3) ◽  
pp. 307-312
Author(s):  
Mine Dosay-Akbulut
Keyword(s):  
Human Genome ◽  
Human Disease ◽  
Rna Splicing ◽  
Messenger Rna ◽  
Developmental Disorders ◽  
Regulation Of Gene Expression ◽  
Medical Science ◽  
Intronless Genes ◽  
Different Types ◽  
Extra Difficulty

In the maturation mechanism of a messenger RNA, splicing play an important role with removing the noncoding introns and ligating the coding exons. Alternative splicing (AS) gives an extra difficulty to this mechanism and to the regulation of gene expression. The possible disturbing in the alternative RNA splicing mechanism can be a reason to several diseases like cancers and neurodegenerative disorders. Intronless genes (IGs) are seen in almost 3% of the human genome. Functionality of IGs has an important role in signal transduction genes and related regulatory proteins. This diversity can be reason to IG-associated diseases, especially neuropathies, developmental disorders, and cancer. The retroelements can be seen in almost half of the human genome. The known informations indicate that insertion of retroelement into exons and introns of genes promote different types of genetic disease, including cancer. The retroelement connected mutagenesis cause to fifty different types of human disease. The molecular informations and bioinformatic analyses can be used to explain the connection with splicing mutations and genetic mechanisms of several different human disease and understanding of this mechanism play an important role in the formation of treatment programme against to these diseases.Bangladesh Journal of Medical Science Vol.15(3) 2016 p.307-312

The heat shock response: A case study of chromatin dynamics in gene regulation

2013 ◽  
Vol 91 (1) ◽  
pp. 42-48 ◽  
Author(s):  
Sheila S. Teves ◽  
Steven Henikoff
Keyword(s):  
Gene Expression ◽  
Gene Regulation ◽  
Heat Shock ◽  
Heat Shock Response ◽  
Control Of Gene Expression ◽  
Pol Ii ◽  
Chromatin Dynamics ◽  
Regulatory Processes ◽  
Shock Response ◽  
Rate Limiting

Recent studies in transcriptional regulation using the Drosophila heat shock response system have elucidated many of the dynamic regulatory processes that govern transcriptional activation and repression. The classic view that the control of gene expression occurs at the point of RNA polymerase II (Pol II) recruitment is now giving way to a more complex outlook of gene regulation. Promoter chromatin dynamics coordinate with transcription factor binding to maintain the promoters of active genes accessible. For a large number of genes, the rate-limiting step in Pol II progression occurs during its initial elongation, where Pol II transcribes 30–50 bp and pauses for further signals. These paused genes have unique genic chromatin architecture and dynamics compared with genes where Pol II recruitment is rate limiting for expression. Further elongation of Pol II along the gene causes nucleosome turnover, a continuous process of eviction and replacement, which suggests a potential mechanism for Pol II transit along a nucleosomal template. In this review, we highlight recent insights into transcription regulation of the heat shock response and discuss how the dynamic regulatory processes involved at each transcriptional stage help to generate faithful yet highly responsive gene expression.

scholarly journals Genome expression dynamics reveals parasitism regulatory landscape of the root-knot nematode Meloidogyne incognita and a promoter motif associated with effector genes

2021 ◽  
Author(s):  
Martine Da Rocha ◽  
Caroline Bournaud ◽  
Julie Dazeniere ◽  
Peter Thorpe ◽  
Clement Pellegrin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Meloidogyne Incognita ◽  
Life Stage ◽  
Regulation Of Gene Expression ◽  
Root Knot Nematode ◽  
Root Knot Nematodes ◽  
Control Of Gene Expression ◽  
Precise Control ◽  
Effector Genes ◽  
Spatio Temporal

Root-knot nematodes are the major contributor to the crop losses caused by nematodes. Root-knot nematodes secrete effectors into the plant, derived from two sets of pharyngeal gland cells, to manipulate host physiology and immunity. Successful completion of the life cycle, involving successive molts from egg to adult, covers morphologically and functionally distinct stages and will require precise control of gene expression, including effectors. The details of how root-knot nematodes regulate transcription remain sparse. Here, we report a life stage-specific transcriptome of Meloidogyne incognita. Combined with an available annotated genome, we explore the spatio-temporal regulation of gene expression. We reveal gene expression clusters and predicted functions that accompany the major developmental transitions. Focusing on effectors, we identify a putative cis-regulatory motif associated with expression in the dorsal glands: providing an insight into effector regulation. We combine the presence of this motif with several other criteria to predict a novel set of putative dorsal gland effectors. Finally, we show this motif, and thereby its utility, is broadly conserved across the Meloidogyne genus and termed it Mel-DOG. Taken together, we provide the first genome-wide analysis of spatio-temporal gene expression in a root-knot nematode, and identify a new set of candidate effector genes that will guide future functional analyses.

scholarly journals Removal of H3K27me3 by JMJ Proteins Controls Plant Development and Environmental Responses in Arabidopsis

2021 ◽  
Vol 12 ◽  
Author(s):  
Nobutoshi Yamaguchi
Keyword(s):  
Gene Expression ◽  
Plant Development ◽  
Transcriptional Repression ◽  
Target Genes ◽  
Regulation Of Gene Expression ◽  
Histone H3 ◽  
Control Of Gene Expression ◽  
Precise Control ◽  
Repressive Histone Modification ◽  
Environmental Responses

Trimethylation of histone H3 lysine 27 (H3K27me3) is a highly conserved repressive histone modification that signifies transcriptional repression in plants and animals. In Arabidopsis thaliana, the demethylation of H3K27 is regulated by a group of JUMONJI DOMAIN-CONTANING PROTEIN (JMJ) genes. Transcription of JMJ genes is spatiotemporally regulated during plant development and in response to the environment. Once JMJ genes are transcribed, recruitment of JMJs to target genes, followed by demethylation of H3K27, is critically important for the precise control of gene expression. JMJs function synergistically and antagonistically with transcription factors and/or other epigenetic regulators on chromatin. This review summarizes the latest advances in our understanding of Arabidopsis H3K27me3 demethylases that provide robust and flexible epigenetic regulation of gene expression to direct appropriate development and environmental responses in plants.

scholarly journals Nutritional Regulation of Gene Expression: Carbohydrate-, Fat- and Amino Acid-Dependent Modulation of Transcriptional Activity

2019 ◽  
Vol 20 (6) ◽  
pp. 1386 ◽  
Author(s):  
Diego Haro ◽  
Pedro Marrero ◽  
Joana Relat
Keyword(s):  
Gene Expression ◽  
Amino Acid ◽  
Molecular Mechanisms ◽  
Metabolic Diseases ◽  
Regulation Of Gene Expression ◽  
Peroxisome Proliferator ◽  
Nutritional Regulation ◽  
Control Of Gene Expression ◽  
Nutritional Interventions ◽  
Precise Control

The ability to detect changes in nutrient levels and generate an adequate response to these changes is essential for the proper functioning of living organisms. Adaptation to the high degree of variability in nutrient intake requires precise control of metabolic pathways. Mammals have developed different mechanisms to detect the abundance of nutrients such as sugars, lipids and amino acids and provide an integrated response. These mechanisms include the control of gene expression (from transcription to translation). This review reports the main molecular mechanisms that connect nutrients’ levels, gene expression and metabolism in health. The manuscript is focused on sugars’ signaling through the carbohydrate-responsive element binding protein (ChREBP), the role of peroxisome proliferator-activated receptors (PPARs) in the response to fat and GCN2/activating transcription factor 4 (ATF4) and mTORC1 pathways that sense amino acid concentrations. Frequently, alterations in these pathways underlie the onset of several metabolic pathologies such as obesity, insulin resistance, type 2 diabetes, cardiovascular diseases or cancer. In this context, the complete understanding of these mechanisms may improve our knowledge of metabolic diseases and may offer new therapeutic approaches based on nutritional interventions and individual genetic makeup.

scholarly journals Colocalization and Redistribution of Dishevelled and Actin during WNT-Induced Mesenchymal Morphogenesis

2000 ◽  
Vol 149 (7) ◽  
pp. 1433-1442 ◽  
Author(s):  
Monica A. Torres ◽  
W. James Nelson
Keyword(s):  
Gene Expression ◽  
Wnt Signaling ◽  
Signaling Pathway ◽  
Wnt Signaling Pathway ◽  
Cell Spreading ◽  
Mesenchymal Cell ◽  
Mouse Kidney ◽  
Cell Morphogenesis ◽  
Embryonic Mouse ◽  
Stimulation Of

Activation of the Wnt signaling pathway is important for induction of gene expression and cell morphogenesis throughout embryonic development. We examined the subcellular localization of dishevelled, the immediate downstream component from the Wnt receptor, in the embryonic mouse kidney. Using immunofluorescence staining, confocal microscopy, and coimmunoprecipitation experiments, we show that dishevelled associates with actin fibers and focal adhesion plaques in metanephric mesenchymal cells. Stimulation of Wnt signaling leads to profound changes in metanephric mesenchymal cell morphology, including disruption of the actin cytoskeleton, increased cell spreading, and increased karyokinesis. Upon activation of Wnt signaling, dishevelled also accumulates in and around the nucleus. Casein kinase Iε colocalizes with dishevelled along actin fibers and in the perinuclear region, whereas axin and GSK-3 are only present around the nucleus. These data indicate a branched Wnt signaling pathway comprising a canonical signal that targets the nucleus and gene expression, and another signal that targets the cytoskeleton and regulates cell morphogenesis.

scholarly journals A mechanism for RNA–RNA splicing and a model for the control of gene expression

1979 ◽  
Vol 34 (2) ◽  
pp. 173-188 ◽  
Author(s):  
Vincent Murray ◽  
Robin Holliday
Keyword(s):  
Gene Expression ◽  
Rna Splicing ◽  
Rna Structure ◽  
Control Of Gene Expression ◽  
Double Stranded Rna ◽  
Exact Location ◽  
Exon Ligation ◽  
Intervening Sequences ◽  
Regulation Of Synthesis ◽  
Precursor Mrna

SUMMARYA mechanism for RNA–RNA splicing is proposed. A species of RNA (‘splicer’ RNA) hybridizes to precursor mRNA across the splice point. This hybridization can be with intron or exon sequences or both. The double-stranded RNA structure precisely indicates to the splicing enzymes the exact location for exon ligation.A model for the control of gene expression is presented. The regulation of synthesis of different splicer RNAs will also control which precursor mRNA molecules are spliced. The removal of intervening sequences from a precursor mRNA molecule could be both a signal for that molecule to be transported to the cytoplasm and a means of allowing gene expression.

scholarly journals IWS1 phosphorylation by AKT3 controls nuclear export of type I IFN mRNAs and sensitivity to oncolytic viral infection, by regulating the alternative RNA splicing of U2AF2

2020 ◽  
Author(s):  
Georgios I. Laliotis ◽  
Adam D. Kenney ◽  
Evangelia Chavdoula ◽  
Arturo Orlacchio ◽  
Abdul K. Kaba ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Viral Infection ◽  
Nuclear Export ◽  
Rna Splicing ◽  
Proper Function ◽  
Type I ◽  
Exon 2 ◽  
Type I Ifns ◽  
Intronless Genes ◽  
In Cells

AbstractType I IFNs orchestrate the antiviral response. Interestingly, IFNA1 and IFNB1 genes are naturally intronless. Based on previous work, the splicing factor U2 Associated Factor 65 (U2AF65), encoded by U2AF2, and pre-mRNA Processing factor 19 (Prp19) function on the Cytoplasmic Accumulation Region Elements (CAR-E), affecting the nuclear export of intronless genes. We have previously shown that the loss of IWS1 phosphorylation by AKT3, promotes the alternative RNA splicing of U2AF2, resulting in novel transcripts lacking exon 2. This exon encodes part of the Serine-Rich (RS) domain of U2AF65, which is responsible for its binding with Prp19. Here, we show that IWS1 phosphorylation and the U2AF2 RNA splicing pattern affect the nuclear export of introless mRNAs. We also demonstrate that the same axis is required for the proper function of the CAR-Es. Mechanistically, whereas both U2AF65 isoforms bind CAR-E, the recruitment of Prp19 occurs only in cells expressing phosphorylated IWS, promoting intronless genes export. Moreover, analysis of Lung adenocarcinoma patients showed that high p-IWS1 activity correlates with the assembly of the U2AF65/Prp19 complex and export of intronless genes, in vivo. Accordingly, the expression of type I IFNs was decreased in cells deficient in IWS1 phosphorylation and the viral infection was increased. Furthermore, following infection with oncolytic virus, we observed reduced activation of p-STAT1 and expression of Interferon Stimulated Genes (ISG), in cells stimulated by shIWS1-derived supernatant, or cells treated with the pan-AKT inhibitor, MK2206. Consistently, killing curves and apoptosis assays after infection with oncolytic viruses, revealed increased susceptibility upon the loss of IWS1, with subsequent activation of Caspase-mediated death. The treatment of the lung adenocarcinoma cells with MK2206, phenocopied the loss of IWS1 phosphorylation. These data identify a novel mechanism by which the AKT/p-IWS1 axis, by hijacking the epigenetic regulation of RNA splicing and processing, contributes to the resistance to oncolytic viral infection, suggesting that combined inhibition of the splicing machinery and AKT/p-IWS1 signals would sensitize tumors to oncolytic viral treatment.

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