scholarly journals Autoregulated expression of the yeast INO2 and INO4 helix-loop-helix activator genes effects cooperative regulation on their target genes.

1995 ◽  
Vol 15 (3) ◽  
pp. 1709-1715 ◽  
Author(s):  
B P Ashburner ◽  
J M Lopes
Keyword(s):  
Gene Expression ◽  
Mutant Strain ◽  
Target Genes ◽  
Transcriptional Level ◽  
Biosynthetic Genes ◽  
Yeast Saccharomyces Cerevisiae ◽  
Helix Loop Helix ◽  
Dual Mechanism ◽  
Cat Gene ◽  
Cat Expression

In the yeast Saccharomyces cerevisiae, the phospholipid biosynthetic genes are highly regulated at the transcriptional level in response to the phospholipid precursors inositol and choline. In the absence of inositol and choline (derepressing), the products of the INO2 and INO4 genes form a heteromeric complex which binds to a 10-bp element, upstream activation sequence INO (UASINO), in the promoters of the phospholipid biosynthetic genes to activate their transcription. In the presence of inositol and choline (repressing), the product of the OPI1 gene represses transcription dictated by the UASINO element. Curiously, we identified a UASINO-like element in the promoters of both the INO2 and INO4 genes. The presence of the UASINO element in these two promoters suggested that the mechanism for the inositol-choline response would involved regulating expression of the two activator genes. Using a cat reporter gene, we find that INO2-cat expression was regulated 12-fold in response to inositol and choline but that INO4-cat was constitutively expressed. We further observed that INO2-cat was not expressed in either an ino2 or an ino4 mutant strain and was constitutively overexpressed in an opi1 mutant strain. Expression of the INO4-cat gene was affected only by mutation in the INO4 gene itself. Therefore, INO2-cat transcription is regulated by the products of both the INO2 and INO4 genes whereas INO4 must interact with another protein to activate its own transcription. Our data show that derepression of phospholipid biosynthetic gene expression involves two mechanisms: increasing the levels of the INO2 and INO4 gene products and inactivating the OPI1-mediated repression mechanism. We propose a model suggesting that this dual mechanism of regulation accounts for the observed cooperative stimulation of IN01 and CH01 gene expression (phospholipids biosynthetic genes).

scholarly journals Cross-Kingdom Regulation by Plant microRNAs Provides Novel Insight into Gene Regulation

2020 ◽  
Author(s):  
Abdul Fatah A Samad ◽  
Mohd Farizal Kamaroddin ◽  
Muhammad Sajad
Keyword(s):  
Gene Expression ◽  
Target Genes ◽  
Current Knowledge ◽  
Circulatory System ◽  
Dietary Therapy ◽  
Transcriptional Level ◽  
Plant Mirnas ◽  
Health Issues ◽  
Plant Mirna ◽  
Potential Applications

ABSTRACT microRNAs (miRNAs) are well known as major players in mammalian and plant genetic systems that act by regulating gene expression at the post-transcriptional level. These tiny molecules can regulate target genes (mRNAs) through either cleavage or translational inhibition. Recently, the discovery of plant-derived miRNAs showing cross-kingdom abilities to regulate mammalian gene expression has prompted exciting discussions among researchers. After being acquired orally through the diet, plant miRNAs can survive in the digestive tract, enter the circulatory system, and regulate endogenous mRNAs. Here, we review current knowledge regarding the cross-kingdom mechanisms of plant miRNAs, related controversies, and potential applications of these miRNAs in dietary therapy, which will provide new insights for plant miRNA investigations related to health issues in humans.

scholarly journals Carbohydrate Response Element Binding Protein Gene Expression Is Positively Regulated by Thyroid Hormone

Endocrinology ◽  
2009 ◽  
Vol 150 (7) ◽  
pp. 3417-3424 ◽  
Author(s):  
Koshi Hashimoto ◽  
Emi Ishida ◽  
Shunichi Matsumoto ◽  
Shuichi Okada ◽  
Masanobu Yamada ◽  
...  
Keyword(s):  
Gene Expression ◽  
Thyroid Hormone ◽  
Target Genes ◽  
Binding Protein ◽  
Gene Promoter ◽  
Direct Repeat ◽  
Transcriptional Level ◽  
Hepatic Lipogenesis ◽  
Response Element ◽  
Element Binding Protein

The molecular mechanism of thyroid hormone (TH) effects to fatty acid metabolism in liver is yet to be clear. The carbohydrate response element-binding protein (ChREBP) as well as sterol response element-binding protein (SREBP)-1c plays a pivotal role in hepatic lipogenesis. Both SREBP-1c and ChREBP are target genes of liver X receptors (LXRs). Because LXRs and TH receptors (TRs) cross talk mutually in many aspects of transcription, we examined whether TRs regulate the mouse ChREBP gene expression. In the current study, we demonstrated that TH up-regulated mouse ChREBP mRNA and protein expression in liver. Run-on and luciferase assays showed that TH and TR-β1 positively regulated the ChREBP gene transcription. The mouse ChREBP gene promoter contains two direct repeat-4 sites (LXRE1 and LXRE2) and EMSAs demonstrated that LXR-α and TR-β1 prefer to bind LXRE1 and LXRE2, respectively. The direct repeat-4 deletion and LXRE2 mutants of the promoter deteriorate the positive regulation by TR-β1, indicating that LXRE2 is functionally important for the regulation. We also showed that human ChREBP gene expression and promoter activities were up-regulated by TH. These data suggest that ChREBP mRNA expression is positively regulated by TR-β1 and TH at the transcriptional level in mammals. This novel observation indicates that TH fine-tunes hepatic lipogenesis via regulating SREBP-1c and ChREBP gene expression reciprocally.

scholarly journals Bio Immune(G)ene Medicine and the Use of miRNAs to Regulate the Cell

2018 ◽  
Vol 1 (2) ◽  
Keyword(s):  
Gene Expression ◽  
Target Genes ◽  
Allergic Diseases ◽  
Degradation Process ◽  
Transcriptional Level ◽  
Collateral Damage ◽  
Rna Molecules ◽  
The Past ◽  
Needed Information ◽  
Non Coding Rna

MicroRNAs (miRNAs or miRs) are a type of non-coding RNA molecules that regulate the gene expression in a negative way, by downregulating the gene expression mainly at the post-transcriptional level, either by the mRNA degradation process or the inhibition of the translation. The role that many miRNAs play in the pathogenesis of several diseases is well known, such as in the inflammation process, in several steps of the oncogenesis or the metabolism of several virus and bacteria among many others. One of the main limitations in the therapeutic use of miRNAs is the ability to reach the target, as well as doing so without causing any collateral damage. One microRNA can indeed regulate up to 200 target-genes, and one gene can be influenced by a lot of different microRNAs. This is the purpose of the Bio Immune(G)ene Medicine: to achieve the cell without harm, use all the molecular resources available, especially epigenetic with the microRNAs, and to restore the cell homeostasis. The Bio Immune(G)ene Medicine only seeks to play a regulatory biomimetic role, to give the cell the needed information for its own right regulation. Our experience in cell regulation for the past few years has shown the way to fight, for instance, against the deleterious effects of viruses or bacteria in the lymphocytes, also at the background of many autoimmune or allergic diseases, as well as to regulate many other pathological processes. To fulfil this purpose, nanobiotechnology is used to reach the targets; we thus introduce very low doses of miRNAs in nano compounds with the aim to promote the regulation of the main signalling pathways disturbed in a given pathology.

scholarly journals Identification and Evaluation of Reference Genes for Normalization of Gene Expression in Developmental Stages, Sexes, and Tissues of Diaphania caesalis (Lepidoptera, Pyralidae)

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Zheng Wang ◽  
Qianqian Meng ◽  
Xi Zhu ◽  
Shiwei Sun ◽  
Aiqin Liu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Reference Genes ◽  
Target Gene ◽  
Target Genes ◽  
Developmental Stages ◽  
Expression Profiles ◽  
Transcriptional Level ◽  
Internal Reference ◽  
Target Gene Expression ◽  
Qrt Pcr

Abstract Diaphania caesalis (Walker) is an important boring insect mainly distributed in subtropical and tropical areas and attacked tropical woody grain crops, such as starchy plants of Artocarpus. Quantitative real-time polymerase chain reaction (qRT-PCR) is a powerful approach for investigating target genes expression profiles at the transcriptional level. However, the identification and selection of internal reference genes, which is often overlooked, is the most vital step before the analysis of target gene expression by qRT-PCR. So far, the reliable internal reference genes under a certain condition of D. caesalis have not been investigated. Therefore, this study evaluated the expression stability of eight candidate reference genes including ACT, β-TUB, GAPDH, G6PDH, RPS3a, RPL13a, EF1α, and EIF4A in different developmental stages, tissues and sexes using geNorm, NormFinder and BestKeeper algorithms. To verify the stability of the recommended internal reference genes, the expression levels of DcaeOBP5 were analyzed under different treatment conditions. The results indicated that ACT, RPL13a, β-TUB, RPS3a, and EF1α were identified as the most stable reference genes for further studies on target gene expression involving different developmental stages of D. caesalis. And ACT and EIF4A were recommended as stable reference genes for different tissues. Furthermore, ACT, EF1α, and RPS3a were ranked as the best reference genes in different sexes based on three algorithms. Our research represents the critical first step to normalize qRT-PCR data and ensure the accuracy of expression of target genes involved in phylogenetic and physiological mechanism at the transcriptional level in D. caesalia.

scholarly journals PQN-59 antagonizes microRNA-mediated repression and functions in stress granule formation during C. elegans development

2021 ◽  
Author(s):  
Christopher Martin Hammell ◽  
Colleen Carlston ◽  
Robin Weinmann ◽  
Natalia Stec ◽  
Simona Abbatemarco ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Fate ◽  
Intracellular Transport ◽  
Target Genes ◽  
Protein Translation ◽  
Transcriptional Level ◽  
Temporal Patterning ◽  
Granule Formation ◽  
C Elegans ◽  
Stable Pattern

microRNAs (miRNAs) are potent regulators of gene expression that function in a variety of developmental and physiological processes by dampening the expression of their target genes at a post-transcriptional level. In many gene regulatory networks (GRNs), miRNAs function in a switch-like manner whereby their expression and activity elicit a transition from one stable pattern of gene expression to a distinct, equally stable pattern required to define a nascent cell fate. While the importance of miRNAs that function in this capacity are clear, we have less of an understanding of the cellular factors and mechanisms that ensure the robustness of this form of regulatory bistability. In a screen to identify suppressors of temporal patterning phenotypes that result from ineffective miRNA-mediated target repression during  C. elegans  development, we identified  pqn-59,  an ortholog of human UBAP2L, as a novel factor that antagonizes the activities of multiple heterochronic miRNAs.  Specifically, we find that depletion of  pqn-59 can restore normal development in animals with reduced miRNA activity. Importantly, inactivation of  pqn-59  is not sufficient to bypass the requirement of these regulatory RNAs within the heterochronic GRN. The  pqn-59  gene encodes an abundant, cytoplasmically localized and unstructured protein that harbors three essential “prion-like” domains.  These domains exhibit LLPS properties  in vitro  and normally function to limit PQN-59 diffusion in the cytoplasm  in vivo . Like human UBAP2L, PQN-59’s localization becomes highly dynamic during stress conditions where it re-distributes to cytoplasmic stress granules and is important for their formation. Proteomic analysis of PQN-59 complexes from embryonic extracts indicates that PQN-59 and human UBAP2L interact with orthologous cellular components involved in RNA metabolism and promoting protein translation and that PQN-59 additionally interacts with proteins involved in transcription and intracellular transport. Finally, we demonstrate that  pqn-59  depletion results in the stabilization of several mature miRNAs (including those involved in temporal patterning) without altering steady-state pre-miRNAs levels indicating that PQN-59 may ensure the bistability of some GRNs that require miRNA functions by promoting miRNA turnover and, like UBAP2L, enhancing protein translation.

scholarly journals Diversity and Versatility in Small RNA-Mediated Regulation in Bacterial Pathogens

2021 ◽  
Vol 12 ◽  
Author(s):  
Brice Felden ◽  
Yoann Augagneur
Keyword(s):  
Gene Expression ◽  
High Throughput Screening ◽  
Regulatory Networks ◽  
Target Genes ◽  
Bacterial Pathogens ◽  
Regulation Of Gene Expression ◽  
Transcriptional Level ◽  
Large Set ◽  
Bacterial Gene ◽  
Bacterial Gene Expression

Bacterial gene expression is under the control of a large set of molecules acting at multiple levels. In addition to the transcription factors (TFs) already known to be involved in global regulation of gene expression, small regulatory RNAs (sRNAs) are emerging as major players in gene regulatory networks, where they allow environmental adaptation and fitness. Developments in high-throughput screening have enabled their detection in the entire bacterial kingdom. These sRNAs influence a plethora of biological processes, including but not limited to outer membrane synthesis, metabolism, TF regulation, transcription termination, virulence, and antibiotic resistance and persistence. Almost always noncoding, they regulate target genes at the post-transcriptional level, usually through base-pair interactions with mRNAs, alone or with the help of dedicated chaperones. There is growing evidence that sRNA-mediated mechanisms of actions are far more diverse than initially thought, and that they go beyond the so-called cis- and trans-encoded classifications. These molecules can be derived and processed from 5' untranslated regions (UTRs), coding or non-coding sequences, and even from 3' UTRs. They usually act within the bacterial cytoplasm, but recent studies showed sRNAs in extracellular vesicles, where they influence host cell interactions. In this review, we highlight the various functions of sRNAs in bacterial pathogens, and focus on the increasing examples of widely diverse regulatory mechanisms that might compel us to reconsider what constitute the sRNA.

scholarly journals Modulation of Bacterial Fitness and Virulence Through Antisense RNAs

2021 ◽  
Vol 10 ◽  
Author(s):  
Jess A. Millar ◽  
Rahul Raghavan
Keyword(s):  
Gene Expression ◽  
Target Genes ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Transcriptional Level ◽  
Antisense Rnas ◽  
Expression Control ◽  
Gene Expression Control ◽  
Bacterial Fitness ◽  
Regulatory Rnas

Regulatory RNAs contribute to gene expression control in bacteria. Antisense RNAs (asRNA) are a class of regulatory RNAs that are transcribed from opposite strands of their target genes. Typically, these untranslated transcripts bind to cognate mRNAs and rapidly regulate gene expression at the post-transcriptional level. In this article, we review asRNAs that modulate bacterial fitness and increase virulence. We chose examples that underscore the variety observed in nature including, plasmid- and chromosome-encoded asRNAs, a riboswitch-regulated asRNA, and asRNAs that require other RNAs or RNA-binding proteins for stability and activity. We explore how asRNAs improve bacterial fitness and virulence by modulating plasmid acquisition and maintenance, regulating transposon mobility, increasing resistance against bacteriophages, controlling flagellar production, and regulating nutrient acquisition. We conclude with a brief discussion on how this knowledge is helping to inform current efforts to develop new therapeutics.

Exogenous application of RNAs as a silencing tool for discovering gene function.

2021 ◽  
pp. 14-24
Author(s):  
Barbara Molesini ◽  
Tiziana Pandolfini
Keyword(s):  
Gene Expression ◽  
Gene Function ◽  
Rna Silencing ◽  
Target Genes ◽  
Specific Gene ◽  
Transcriptional Level ◽  
Fruit Setting ◽  
Organ Tissue ◽  
Specific Regulation ◽  
Time Specific

Abstract This chapter focuses on the importance of the RNA silencing technique in unraveling the function of genes by inhibiting gene expression at the post-transcriptional level, and is particularly appropriate for studying developmental processes such as fruit setting and growth that require a tight organ/tissue and time-specific regulation of the expression of target genes. Some methods used for establishing the function of a specific gene altering gene expression at either the genomic or post-transcriptional level are also presented.

Phorbol ester enhances human immunodeficiency virus-promoted gene expression and acts on a repeated 10-base-pair functional enhancer element

1987 ◽  
Vol 7 (10) ◽  
pp. 3759-3766
Author(s):  
J D Kaufman ◽  
G Valandra ◽  
G Roderiquez ◽  
G Bushar ◽  
C Giri ◽  
...  
Keyword(s):  
Gene Expression ◽  
Human Immunodeficiency Virus ◽  
T Cell ◽  
Cell Lines ◽  
T Cell Activation ◽  
Potent Inducer ◽  
Enhancer Element ◽  
Immunodeficiency Virus ◽  
Cat Gene ◽  
Cat Expression

T-cell activation pathways are involved in the regulation of human immunodeficiency virus (HIV) expression. Phorbol 12-myristate 13-acetate (PMA) is a potent inducer of T-cell immune functions and has recently been demonstrated to increase viral replication in cell lines infected with HIV. To define sequences required for viral induction by PMA. T-cell lines were transiently transfected with viral long terminal repeat (LTR) sequences directing chloramphenicol acetyltransferase (CAT) gene expression. PMA added to transfected cell cultures 24 h before harvest reproducibly increased both CAT mRNA and enzyme expression 2- to 2-fold. Sequences necessary for basal and PMA-induced levels of CAT expression were determined by deletion and enhancer reconstitution constructs with fragments and oligonucleotides from the original LTR-CAT expression plasmid. PMA-inducible and basal activity required tandem repeats of a core enhancer element (GGGACTTTCC) located in the LTR between -105 and -82 relative to the RNA start site. The enhancerlike sequence could be inserted at a site distant to the CAT gene open reading frame and functioned in a position- and orientation-independent manner. The data thus define a transcriptionally active regulatory-enhancer element critical to the control of HIV gene expression.

scholarly journals Phorbol ester enhances human immunodeficiency virus-promoted gene expression and acts on a repeated 10-base-pair functional enhancer element.

1987 ◽  
Vol 7 (10) ◽  
pp. 3759-3766 ◽  
Author(s):  
J D Kaufman ◽  
G Valandra ◽  
G Roderiquez ◽  
G Bushar ◽  
C Giri ◽  
...  
Keyword(s):  
Gene Expression ◽  
Human Immunodeficiency Virus ◽  
T Cell ◽  
Cell Lines ◽  
T Cell Activation ◽  
Potent Inducer ◽  
Enhancer Element ◽  
Immunodeficiency Virus ◽  
Cat Gene ◽  
Cat Expression

T-cell activation pathways are involved in the regulation of human immunodeficiency virus (HIV) expression. Phorbol 12-myristate 13-acetate (PMA) is a potent inducer of T-cell immune functions and has recently been demonstrated to increase viral replication in cell lines infected with HIV. To define sequences required for viral induction by PMA. T-cell lines were transiently transfected with viral long terminal repeat (LTR) sequences directing chloramphenicol acetyltransferase (CAT) gene expression. PMA added to transfected cell cultures 24 h before harvest reproducibly increased both CAT mRNA and enzyme expression 2- to 2-fold. Sequences necessary for basal and PMA-induced levels of CAT expression were determined by deletion and enhancer reconstitution constructs with fragments and oligonucleotides from the original LTR-CAT expression plasmid. PMA-inducible and basal activity required tandem repeats of a core enhancer element (GGGACTTTCC) located in the LTR between -105 and -82 relative to the RNA start site. The enhancerlike sequence could be inserted at a site distant to the CAT gene open reading frame and functioned in a position- and orientation-independent manner. The data thus define a transcriptionally active regulatory-enhancer element critical to the control of HIV gene expression.

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