miRNAs may play a major role in the control of gene expression in key pathobiological processes in Chagas disease cardiomyopathy

Chronic Chagas disease cardiomyopathy (CCC), an especially aggressive inflammatory dilated cardiomyopathy caused by lifelong infection with the protozoan Trypanosoma cruzi, is a major cause of cardiomyopathy in Latin America. Although chronic myocarditis may play a major pathogenetic role, little is known about the molecular mechanisms responsible for its severity. The aim of this study is to study the genes and microRNAs expression in tissues and their connections in regards to the pathobiological processes. To do so, we integrated for the first time global microRNA and mRNA expression profiling from myocardial tissue of CCC patients employing pathways and network analyses. We observed an enrichment in biological processes and pathways associated with the immune response and metabolism. IFNγ, TNF and NFkB were the top upstream regulators. The intersections between differentially expressed microRNAs and differentially expressed target mRNAs showed an enrichment in biological processes such as Inflammation, inflammation, Th1/IFN-γ-inducible genes, fibrosis, hypertrophy, and mitochondrial/oxidative stress/antioxidant response. MicroRNAs also played a role in the regulation of gene expression involved in the key cardiomyopathy-related processes fibrosis, hypertrophy, myocarditis and arrhythmia. Significantly, a discrete number of differentially expressed microRNAs targeted a high number of differentially expressed mRNAs (>20) in multiple processes. Our results suggest that miRNAs orchestrate expression of multiple genes in the major pathophysiological processes in CCC heart tissue. This may have a bearing on pathogenesis, biomarkers and therapy.

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

International Journal of Molecular Sciences ◽

10.3390/ijms20061386 ◽

2019 ◽

Vol 20 (6) ◽

pp. 1386 ◽

Cited By ~ 6

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.

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Amino acid limitation regulates gene expression

Proceedings of The Nutrition Society ◽

10.1017/s0029665199000828 ◽

1999 ◽

Vol 58 (3) ◽

pp. 625-632 ◽

Cited By ~ 29

Author(s):

Alain Bruhat ◽

Céline Jousse ◽

Pierre Fafournoux

Keyword(s):

Gene Expression ◽

Amino Acids ◽

Amino Acid ◽

Molecular Mechanisms ◽

Binding Protein ◽

Regulation Of Gene Expression ◽

Essential Amino Acids ◽

Mrna Levels ◽

Dependent Manner ◽

Control Of Gene Expression

In mammals, the plasma concentration of amino acids is affected by nutritional or pathological conditions. For example, an alteration in the amino acid profile has been reported when there is a deficiency of any one or more of the essential amino acids, a dietary imbalance of amino acids, or an insufficient intake of protein. We examined the role of amino acid limitation in regulating mammalian gene expression. Depletion of arginine, cystine and all essential amino acids leads to induction of insulin-like growth factor-binding protein-1 (IGFBP-1) mRNA and protein expression in a dose-dependent manner. Moreover, exposure of HepG2 cells to amino acids at a concentration reproducing the amino acid concentration found in portal blood of rats fed on a low-protein diet leads to a significantly higher (P < 0·0002) expression of IGFBP-1. Using CCAAT/enhancer-binding protein homologous protein (CHOP) induction by leucine deprivation as a model, we have characterized the molecular mechanisms involved in the regulation of gene expression by amino acids. We have shown that leucine limitation leads to induction of CHOP mRNA and protein. Elevated mRNA levels result from both an increase in the rate of CHOP transcription and an increase in mRNA stability. We have characterized two elements of the CHOP gene that are essential to the transcriptional activation produced by an amino acid limitation. These findings demonstrate that an amino acid limitation, as occurs during dietary protein deficiency, can induce gene expression. Thus, amino acids by themselves can play, in concert with hormones, an important role in the control of gene expression.

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Analysis of pathways and networks influencing the differential expression of genes in coronary artery disease

Archives of Biological Sciences ◽

10.2298/abs1403983l ◽

2014 ◽

Vol 66 (3) ◽

pp. 983-988 ◽

Cited By ~ 1

Author(s):

Hui Li ◽

Xiaolan Zhong ◽

Chaomin Li ◽

Lijing Peng ◽

Wei Liu ◽

...

Keyword(s):

Gene Expression ◽

Coronary Artery Disease ◽

Coronary Artery ◽

Differentially Expressed Genes ◽

Molecular Mechanisms ◽

Gene Expression Omnibus ◽

Differentially Expressed ◽

Hub Genes ◽

Network Analyses ◽

Artery Disease

Coronary artery disease (CAD) is the leading cause of death worldwide. Microarray analysis is a practical approach to study gene transcription changes that may reflect signatures that underlie the pathogenesis of CAD. Using gene expression profile data from the Gene Expression Omnibus database, we identified differentially expressed genes that can contribute to the pathology of CAD. Further pathway and network analyses were also implemented to identify pathways and hub genes related to the disease. We observed 466 downregulated and 560 upregulated genes. The ribosome pathway was the most significantly over-represented pathway with differentially expressed genes. Over 35% of the genes in this pathway were downregulated. Hub genes in the network, such as IL7R, FYN, CALM1 ESR1 and PLCG1, may play crucial roles in the pathogenesis of CAD. Our results facilitate the identification of molecular mechanisms that underlie CAD.

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NMDAR-mediated transcriptional control of gene expression in the specification of interneuron subtype identity

10.1101/2020.06.10.144295 ◽

2020 ◽

Cited By ~ 2

Author(s):

Vivek Mahadevan ◽

Apratim Mitra ◽

Yajun Zhang ◽

Areg Peltekian ◽

Ramesh Chittajallu ◽

...

Keyword(s):

Gene Expression ◽

Transcriptional Control ◽

Molecular Mechanisms ◽

Regulation Of Gene Expression ◽

Medial Ganglionic Eminence ◽

Membrane Excitability ◽

Control Of Gene Expression ◽

Road Map ◽

Physiological Properties ◽

Nmdar Subunit

AbstractMedial ganglionic eminence (MGE)-derived parvalbumin (PV)+, somatostatin (SST)+ and Neurogliaform (NGFC)-type cortical and hippocampal interneurons, have distinct molecular, anatomical and physiological properties. However, the molecular mechanisms regulating their diversity remain poorly understood. Here, via single-cell transcriptomics, we show that the obligate NMDA-type glutamate receptor (NMDAR) subunit gene Grin1 mediates subtype-specific transcriptional regulation of gene expression in MGE-derived interneurons, leading to altered subtype identities. Notably, MGE-specific conditional Grin1 loss results in a systemic downregulation of diverse transcriptional, synaptogenic and membrane excitability regulatory programs. These widespread gene expression abnormalities mirror aberrations that are typically associated with neurodevelopmental disorders, particularly schizophrenia. Our study hence provides a road map for the systematic examination of NMDAR signaling in interneuron subtypes, revealing potential MGE-specific genetic targets that could instruct future therapies of psychiatric disorders.

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The function of KptA/Tpt1 gene – a minor review

Functional Plant Biology ◽

10.1071/fp19159 ◽

2020 ◽

Vol 47 (7) ◽

pp. 577

Author(s):

Shiquan Yang ◽

Gaoyi Qu ◽

Bixia Fu ◽

Feng Yang ◽

Weixian Zeng ◽

...

Keyword(s):

Gene Expression ◽

Essential Role ◽

Molecular Mechanisms ◽

Environmental Changes ◽

Regulation Of Gene Expression ◽

Biological Processes ◽

Trna Splicing ◽

Adp Ribosylation ◽

A Minor ◽

Multicellular Organisms

Rapid response of uni- and multicellular organisms to environmental changes and their own growth is achieved through a series of molecular mechanisms, often involving modification of macromolecules, including nucleic acids, proteins and lipids. The ADP-ribosylation process has ability to modify these different macromolecules in cells, and is closely related to the biological processes, such as DNA replication, transcription, signal transduction, cell division, stress, microbial aging and pathogenesis. In addition, tRNA plays an essential role in the regulation of gene expression, as effector molecules, no-load tRNA affects the overall gene expression level of cells under some nutritional stress. KptA/Tpt1 is an essential phosphotransferase in the process of pre-tRNA splicing, releasing mature tRNA and participating in ADP-ribose. The objective of this review is concluding the gene structure, the evolution history and the function of KptA/Tpt1 from prokaryote to eukaryote organisms. At the same time, the results of promoter elements analysis were also shown in the present study. Moreover, the problems in the function of KptA/Tpt1 that have not been clarified at the present time are summarised, and some suggestions to solve those problems are given. This review presents no only a summary of clear function of KptA/Tpt1 in the process of tRNA splicing and ADP-ribosylation of organisms, but also gives some proposals to clarify unclear problems of it in the future.

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Review of Progress in Predicting Protein Methylation Sites

Current Organic Chemistry ◽

10.2174/1385272823666190723141347 ◽

2019 ◽

Vol 23 (15) ◽

pp. 1663-1670 ◽

Cited By ~ 1

Author(s):

Chunyan Ao ◽

Shunshan Jin ◽

Yuan Lin ◽

Quan Zou

Keyword(s):

Gene Expression ◽

Signal Transduction ◽

Transcriptional Activity ◽

Regulation Of Gene Expression ◽

Protein Methylation ◽

Biological Processes ◽

Post Translational Modification ◽

Regulatory Enzymes ◽

Lysine Residues ◽

Arginine Residues

Protein methylation is an important and reversible post-translational modification that regulates many biological processes in cells. It occurs mainly on lysine and arginine residues and involves many important biological processes, including transcriptional activity, signal transduction, and the regulation of gene expression. Protein methylation and its regulatory enzymes are related to a variety of human diseases, so improved identification of methylation sites is useful for designing drugs for a variety of related diseases. In this review, we systematically summarize and analyze the tools used for the prediction of protein methylation sites on arginine and lysine residues over the last decade.

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Microtubule Dynamics Plays a Vital Role in Plant Adaptation and Tolerance to Salt Stress

International Journal of Molecular Sciences ◽

10.3390/ijms22115957 ◽

2021 ◽

Vol 22 (11) ◽

pp. 5957

Author(s):

Hyun Jin Chun ◽

Dongwon Baek ◽

Byung Jun Jin ◽

Hyun Min Cho ◽

Mi Suk Park ◽

...

Keyword(s):

Gene Expression ◽

Cell Wall ◽

Salt Stress ◽

Differentially Expressed ◽

Differentially Expressed Proteins ◽

Related Gene ◽

Plant Adaptation ◽

Salt Stress Response ◽

Network Analyses ◽

Cell Wall Biogenesis

Although recent studies suggest that the plant cytoskeleton is associated with plant stress responses, such as salt, cold, and drought, the molecular mechanism underlying microtubule function in plant salt stress response remains unclear. We performed a comparative proteomic analysis between control suspension-cultured cells (A0) and salt-adapted cells (A120) established from Arabidopsis root callus to investigate plant adaptation mechanisms to long-term salt stress. We identified 50 differentially expressed proteins (45 up- and 5 down-regulated proteins) in A120 cells compared with A0 cells. Gene ontology enrichment and protein network analyses indicated that differentially expressed proteins in A120 cells were strongly associated with cell structure-associated clusters, including cytoskeleton and cell wall biogenesis. Gene expression analysis revealed that expressions of cytoskeleton-related genes, such as FBA8, TUB3, TUB4, TUB7, TUB9, and ACT7, and a cell wall biogenesis-related gene, CCoAOMT1, were induced in salt-adapted A120 cells. Moreover, the loss-of-function mutant of Arabidopsis TUB9 gene, tub9, showed a hypersensitive phenotype to salt stress. Consistent overexpression of Arabidopsis TUB9 gene in rice transgenic plants enhanced tolerance to salt stress. Our results suggest that microtubules play crucial roles in plant adaptation and tolerance to salt stress. The modulation of microtubule-related gene expression can be an effective strategy for developing salt-tolerant crops.

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Transcription Factors as the “Blitzkrieg” of Plant Defense: A Pragmatic View of Nitric Oxide’s Role in Gene Regulation

International Journal of Molecular Sciences ◽

10.3390/ijms22020522 ◽

2021 ◽

Vol 22 (2) ◽

pp. 522

Author(s):

Noreen Falak ◽

Qari Muhammad Imran ◽

Adil Hussain ◽

Byung-Wook Yun

Keyword(s):

Gene Expression ◽

Transcription Factors ◽

Plant Defense ◽

Systemic Acquired Resistance ◽

Defense Mechanism ◽

Regulation Of Gene Expression ◽

Acquired Resistance ◽

Biological Processes ◽

Genetic Components ◽

Transcriptional Changes

Plants are in continuous conflict with the environmental constraints and their sessile nature demands a fine-tuned, well-designed defense mechanism that can cope with a multitude of biotic and abiotic assaults. Therefore, plants have developed innate immunity, R-gene-mediated resistance, and systemic acquired resistance to ensure their survival. Transcription factors (TFs) are among the most important genetic components for the regulation of gene expression and several other biological processes. They bind to specific sequences in the DNA called transcription factor binding sites (TFBSs) that are present in the regulatory regions of genes. Depending on the environmental conditions, TFs can either enhance or suppress transcriptional processes. In the last couple of decades, nitric oxide (NO) emerged as a crucial molecule for signaling and regulating biological processes. Here, we have overviewed the plant defense system, the role of TFs in mediating the defense response, and that how NO can manipulate transcriptional changes including direct post-translational modifications of TFs. We also propose that NO might regulate gene expression by regulating the recruitment of RNA polymerase during transcription.

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The Role of Translation Initiation Regulation in Haematopoiesis

Comparative and Functional Genomics ◽

10.1155/2012/576540 ◽

2012 ◽

Vol 2012 ◽

pp. 1-10 ◽

Cited By ~ 7

Author(s):

Godfrey Grech ◽

Marieke von Lindern

Keyword(s):

Gene Expression ◽

Translation Initiation ◽

Translational Control ◽

Molecular Mechanisms ◽

Rna Binding ◽

Regulation Of Gene Expression ◽

Mrna Translation ◽

Translation Control ◽

Haematological Disorders

Organisation of RNAs into functional subgroups that are translated in response to extrinsic and intrinsic factors underlines a relatively unexplored gene expression modulation that drives cell fate in the same manner as regulation of the transcriptome by transcription factors. Recent studies on the molecular mechanisms of inflammatory responses and haematological disorders indicate clearly that the regulation of mRNA translation at the level of translation initiation, mRNA stability, and protein isoform synthesis is implicated in the tight regulation of gene expression. This paper outlines how these posttranscriptional control mechanisms, including control at the level of translation initiation factors and the role of RNA binding proteins, affect hematopoiesis. The clinical relevance of these mechanisms in haematological disorders indicates clearly the potential therapeutic implications and the need of molecular tools that allow measurement at the level of translational control. Although the importance of miRNAs in translation control is well recognised and studied extensively, this paper will exclude detailed account of this level of control.

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Abstract 286: Long Noncoding RNAs Are Differentially Expressed in Heart Failure

Circulation Research ◽

10.1161/res.111.suppl_1.a286 ◽

2012 ◽

Vol 111 (suppl_1) ◽

Author(s):

Emma L Robinson ◽

Syed Haider ◽

Hillary Hei ◽

Richard T Lee ◽

Roger S Foo

Keyword(s):

Gene Expression ◽

Heart Failure ◽

Significant Proportion ◽

Differentially Expressed ◽

Rna Seq ◽

Control Of Gene Expression ◽

Failing Heart ◽

Novel Transcripts ◽

Non Coding Rnas

Heart failure comprises of clinically distinct inciting causes but a consistent pattern of change in myocardial gene expression supports the hypothesis that unifying biochemical mechanisms underlie disease progression. The recent RNA-seq revolution has enabled whole transcriptome profiling, using deep-sequencing technologies. Up to 70% of the genome is now known to be transcribed into RNA, a significant proportion of which is long non-coding RNAs (lncRNAs), defined as polyribonucleotides of ≥200 nucleotides. This project aims to discover whether the myocardium expression of lncRNAs changes in the failing heart. Paired end RNA-seq from a 300-400bp library of ‘stretched’ mouse myocyte total RNA was carried out to generate 76-mer sequence reads. Mechanically stretching myocytes with equibiaxial stretch apparatus mimics pathological hypertrophy in the heart. Transcripts were assembled and aligned to reference genome mm9 (UCSC), abundance determined and differential expression of novel transcripts and alternative splice variants were compared with that of control (non-stretched) mouse myocytes. Five novel transcripts have been identified in our RNA-seq that are differentially expressed in stretched myocytes compared with non-stretched. These are regions of the genome that are currently unannotated and potentially are transcribed into non-coding RNAs. Roles of known lncRNAs include control of gene expression, either by direct interaction with complementary regions of the genome or association with chromatin remodelling complexes which act on the epigenome.Changes in expression of genes which contribute to the deterioration of the failing heart could be due to the actions of these novel lncRNAs, immediately suggesting a target for new pharmaceuticals. Changes in the expression of these novel transcripts will be validated in a larger sample size of stretched myocytes vs non-stretched myocytes as well as in the hearts of transverse aortic constriction (TAC) mice vs Sham (surgical procedure without the aortic banding). In vivo investigations will then be carried out, using siLNA antisense technology to silence novel lncRNAs in mice.

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