Dual regulatory effects of non-coding GC-rich elements on the expression of virulence genes in malaria parasites

ABSTRACTThe alarmone ppGpp is a critical regulator of virulence gene expression inFrancisella tularensis. In this intracellular pathogen, ppGpp is thought to work in concert with the putative DNA-binding protein PigR and the SspA protein family members MglA and SspA to control a common set of genes. MglA and SspA form a complex that interacts with RNA polymerase (RNAP), and PigR functions by interacting with the RNAP-associated MglA-SspA complex. Prior work suggested that ppGpp indirectly exerts its regulatory effects inF. tularensisby promoting the accumulation of polyphosphate in the cell, which in turn was required for formation of the MglA-SspA complex. Here we show that inEscherichia coli, neither polyphosphate nor ppGpp is required for formation of the MglA-SspA complex but that ppGpp promotes the interaction between PigR and the MglA-SspA complex. Moreover, we show that polyphosphate kinase, the enzyme responsible for the synthesis of polyphosphate, antagonizes virulence gene expression inF. tularensis, a finding that is inconsistent with the notion that polyphosphate accumulation promotes virulence gene expression in this organism. Our findings identify polyphosphate kinase as a novel negative regulator of virulence gene expression inF. tularensisand support a model in which ppGpp exerts its positive regulatory effects by promoting the interaction between PigR and the MglA-SspA complex.IMPORTANCEInFrancisella tularensis, MglA and SspA form a complex that associates with RNA polymerase to positively control the expression of key virulence genes. The MglA-SspA complex works together with the putative DNA-binding protein PigR and the alarmone ppGpp. PigR functions by interacting directly with the MglA-SspA complex, but how ppGpp exerts its effects was unclear. Prior work indicated that ppGpp acts by promoting the accumulation of polyphosphate, which is required for MglA and SspA to interact. Here we show that formation of the MglA-SspA complex does not require polyphosphate. Furthermore, we find that polyphosphate antagonizes the expression of virulence genes inF. tularensis. Thus, ppGpp does not promote virulence gene expression in this organism through an effect on polyphosphate.

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A Critical Role of Perinuclear Filamentous Actin in Spatial Repositioning and Mutually Exclusive Expression of Virulence Genes in Malaria Parasites

Cell Host & Microbe ◽

10.1016/j.chom.2011.09.013 ◽

2011 ◽

Vol 10 (5) ◽

pp. 451-463 ◽

Cited By ~ 66

Author(s):

Qingfeng Zhang ◽

Yufu Huang ◽

Yilong Zhang ◽

Xiaonan Fang ◽

Aurelie Claes ◽

...

Keyword(s):

Virulence Genes ◽

Critical Role ◽

Filamentous Actin ◽

Malaria Parasites

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Recombination events among virulence genes in malaria parasites are associated with G-quadruplex-forming DNA motifs

BMC Genomics ◽

10.1186/s12864-016-3183-3 ◽

2016 ◽

Vol 17 (1) ◽

Cited By ~ 23

Author(s):

Adam Stanton ◽

Lynne M. Harris ◽

Gemma Graham ◽

Catherine J. Merrick

Keyword(s):

Virulence Genes ◽

Malaria Parasites ◽

Dna Motifs ◽

G Quadruplex

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The Role of Zinc in Thyroid Hormones Metabolism

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831/a000262 ◽

2019 ◽

Vol 89 (1-2) ◽

pp. 80-88 ◽

Cited By ~ 6

Author(s):

Juliana Soares Severo ◽

Jennifer Beatriz Silva Morais ◽

Taynáh Emannuelle Coelho de Freitas ◽

Ana Letícia Pereira Andrade ◽

Mayara Monte Feitosa ◽

...

Keyword(s):

Thyroid Hormones ◽

Scientific Evidence ◽

Thyroid Stimulating Hormone ◽

Zinc Transporters ◽

Serum Concentrations ◽

Metabolic Adaptations ◽

Serum T3 ◽

Regulatory Effects ◽

Shed Light

Abstract. Thyroid hormones play an important role in body homeostasis by facilitating metabolism of lipids and glucose, regulating metabolic adaptations, responding to changes in energy intake, and controlling thermogenesis. Proper metabolism and action of these hormones requires the participation of various nutrients. Among them is zinc, whose interaction with thyroid hormones is complex. It is known to regulate both the synthesis and mechanism of action of these hormones. In the present review, we aim to shed light on the regulatory effects of zinc on thyroid hormones. Scientific evidence shows that zinc plays a key role in the metabolism of thyroid hormones, specifically by regulating deiodinases enzymes activity, thyrotropin releasing hormone (TRH) and thyroid stimulating hormone (TSH) synthesis, as well as by modulating the structures of essential transcription factors involved in the synthesis of thyroid hormones. Serum concentrations of zinc also appear to influence the levels of serum T3, T4 and TSH. In addition, studies have shown that Zinc transporters (ZnTs) are present in the hypothalamus, pituitary and thyroid, but their functions remain unknown. Therefore, it is important to further investigate the roles of zinc in regulation of thyroid hormones metabolism, and their importance in the treatment of several diseases associated with thyroid gland dysfunction.

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Melatonin: a novel strategy for prevention of obesity and fat accumulation in peripheral organs through the improvements of circadian rhythms and antioxidative capacity

Melatonin Research ◽

10.32794/mr11250048 ◽

2020 ◽

Vol 3 (1) ◽

pp. 58-76 ◽

Cited By ~ 1

Author(s):

Bohan Rong ◽

Qiong Wu ◽

Chao Sun

Keyword(s):

Oxidative Stress ◽

Skeletal Muscle ◽

Circadian Rhythms ◽

Regulatory Mechanisms ◽

Antioxidative Capacity ◽

Unicellular Alga ◽

Peripheral Tissues ◽

Peripheral Organs ◽

Regulatory Effects ◽

Novel Strategy

Melatonin is a well-known molecule for its involvement in circadian rhythm regulation and its contribution to protection against oxidative stress in organisms including unicellular alga, animals and plants. Currently, the bio-regulatory effects of melatonin on the physiology of various peripheral tissues have drawn a great attention of scientists. Although melatonin was previously defined as a neurohormone secreted from pineal gland, recently it has been identified that virtually, every cell has the capacity to synthesize melatonin and the locally generated melatonin has multiple pathophysiological functions, including regulations of obesity and metabolic syndromes. Herein, we focus on the effects of melatonin on fat deposition in various peripheral organs/tissues. The two important regulatory mechanisms related to the topic, i.e., the improvements of circadian rhythms and antioxidative capacity will be thoroughly discussed since they are linked to several biomarkers involved in obesity and energy imbalance, including metabolism and immunity. Furthermore, several other functions of melatonin which may serve to prevent or promote obesity and energy dysmetabolism-induced pathological states are also addressed. The organs of special interest include liver, pancreas, skeletal muscle, adipose tissue and the gut microbiota.

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Vibrio harveyi virulence gene expression in vitro and in vivo during infection in black tiger shrimp Penaeus monodon

Diseases of Aquatic Organisms ◽

10.3354/dao03475 ◽

2020 ◽

Vol 139 ◽

pp. 153-160

Author(s):

S Peeralil ◽

TC Joseph ◽

V Murugadas ◽

PG Akhilnath ◽

VN Sreejith ◽

...

Keyword(s):

Gene Expression ◽

Virulence Genes ◽

Vibrio Harveyi ◽

Penaeus Monodon ◽

Challenge Test ◽

Virulence Gene ◽

Economic Losses ◽

Virulence Gene Expression

Luminescent Vibrio harveyi is common in sea and estuarine waters. It produces several virulence factors and negatively affects larval penaeid shrimp in hatcheries, resulting in severe economic losses to shrimp aquaculture. Although V. harveyi is an important pathogen of shrimp, its pathogenicity mechanisms have yet to be completely elucidated. In the present study, isolates of V. harveyi were isolated and characterized from diseased Penaeus monodon postlarvae from hatcheries in Kerala, India, from September to December 2016. All 23 tested isolates were positive for lipase, phospholipase, caseinase, gelatinase and chitinase activity, and 3 of the isolates (MFB32, MFB71 and MFB68) showed potential for significant biofilm formation. Based on the presence of virulence genes, the isolates of V. harveyi were grouped into 6 genotypes, predominated by vhpA+ flaB+ ser+ vhh1- luxR+ vopD- vcrD+ vscN-. One isolate from each genotype was randomly selected for in vivo virulence experiments, and the LD50 ranged from 1.7 ± 0.5 × 103 to 4.1 ± 0.1 × 105 CFU ml-1. The expression of genes during the infection in postlarvae was high in 2 of the isolates (MFB12 and MFB32), consistent with the result of the challenge test. However, in MFB19, even though all genes tested were present, their expression level was very low and likely contributed to its lack of virulence. Because of the significant variation in gene expression, the presence of virulence genes alone cannot be used as a marker for pathogenicity of V. harveyi.

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Post-Transcriptional Regulation of Cardiac Sarcomere Protein Titin Through 3’ Untranslated Regions

Vanderbilt Undergraduate Research Journal ◽

10.15695/vurj.v9i0.3772 ◽

2013 ◽

Vol 9 ◽

Cited By ~ 1

Author(s):

Tara A Shrout

Keyword(s):

Gene Expression ◽

Transcriptional Control ◽

Striated Muscle ◽

Binding Capacity ◽

Structural Features ◽

Neonatal Rat ◽

Regulatory Control ◽

Untranslated Regions ◽

Luciferase Reporter ◽

Regulatory Effects

Titin is the largest known protein in the human body, and forms the backbone of all striated muscle sarcomeres. The elastic nature of titin is an important component of muscle compliance and functionality. A significant amount of energy is expended to synthesize titin, thus we postulate that titin gene expression is under strict regulatory control in order to conserve cellular resources. In general, gene expression is mediated in part by post-transcriptional control elements located within the 5’ and 3’ untranslated regions (UTRs) of mature mRNA. The 3’UTR in particular contains structural features that affect binding capacity to other RNA components, such as MicroRNA, which control mRNA localization, translation, and degradation. The degree and significance of the regulatory effects mediated by two determined variants of titin’s 3’ UTR were evaluated in Neonatal Rat Ventricular Myocyte and Human Embryonic Kidney cell lines. Recombinant plasmids to transfect these cells lines were engineered by insertion of the variant titin 3’UTR 431- and 1047-base pairs sequences into luciferase reporter vectors. Expression due to an unaltered reporter vector served as the control. Quantitative changes in luciferase activity due to the recombinants proportionally represented the effect titin’s respective 3’UTR conferred on downstream post-transcriptional expression relative to the control. The effect due to titin’s shorter 3’UTR sequence was inconclusive; however, results illustrated that titin’s longer 3’UTR sequence caused a 35 percent decrease in protein expression. Secondary structural analysis of the two sequences revealed differential folding patterns that affect the stability and degree of MicroRNA-binding within titin’s variant 3’UTR sequences.

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