The role of the BR-C locus on the expression of genes located at the ecdysone-regulated 3C puff of Drosophila melanogaster

Eukaryotic superfamily (SF) 1 helicases have been implicated in various aspects of RNA metabolism, including transcription, processing, translation, and degradation. Nevertheless, until now, most human SF1 helicases remain poorly understood. Here, we have functionally and biochemically characterized the role of a putative SF1 helicase termed “helicase with zinc-finger,” or HELZ. We discovered that HELZ associates with various mRNA decay factors, including components of the carbon catabolite repressor 4-negative on TATA box (CCR4–NOT) deadenylase complex in human and Drosophila melanogaster cells. The interaction between HELZ and the CCR4–NOT complex is direct and mediated by extended low-complexity regions in the C-terminal part of the protein. We further reveal that HELZ requires the deadenylase complex to mediate translational repression and decapping-dependent mRNA decay. Finally, transcriptome-wide analysis of Helz-null cells suggests that HELZ has a role in the regulation of the expression of genes associated with the development of the nervous system.

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Effect of ecd1 mutation on the expression of genes mapped at the Drosophila melanogaster 3C11-12 intermoult puff

Genetics Research ◽

10.1017/s0016672300030135 ◽

1992 ◽

Vol 59 (1) ◽

pp. 19-26 ◽

Cited By ~ 7

Author(s):

Maria Furia ◽

Pier Paolo D'avino ◽

Filomena A. Digilio ◽

Stefania Crispi ◽

Ennio Giordano ◽

...

Keyword(s):

Drosophila Melanogaster ◽

Steroid Hormone ◽

Temperature Sensitive ◽

Permissive Temperature ◽

Expression Of Genes ◽

High Level

SummaryThe Drosophila melanogasterecd1 mutation causes a severe temperature-sensitive deficiency in the titre of the steroid hormone eedysone. This mutation was used to investigate the role of eedysone in both the transcription of the genes mapped at the 3C11–12 intermoult puff region and the puff formation. Thoroughly synchronized ecd1 larvae were shifted to the non-permissive temperature at various times of the development; after 24 or 48 h, the levels of the transcripts derived from Sgs-4, Pig-1 and ng-1, the three genes located at the 3C11–12 polytene bands, were determined. The results showed that the levels of the transcripts encoded by Pig-1 and ng-1 are unaffected by the drop in the ecdysone titre occurring in non-permissive conditions whereas the amount of Sgs-4 mRNA is greatly reduced. These data clearly indicate that transcription of the three genes mapped within the puff region is affected differently by the hormone. Furthermore, ecd1 larvae cultured at the non-permissive temperature show a prominent puff at the 3C11–12 polytene bands, indicating that eedysone is not essential for puff induction and that puff size is not simply correlated with high-level Sgs-4 transcription.

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New trends in the pharmacological intervention of PPARs in obesity: Role of natural and synthetic compounds_

Current Medicinal Chemistry ◽

10.2174/1570162x18666201123114934 ◽

2020 ◽

Vol 28 ◽

Author(s):

Seyed Mohammad Nabavi ◽

Kasi Pandima Devi ◽

Sethuraman Sathya ◽

Ana Sanches-Silva ◽

Listos Joanna ◽

...

Keyword(s):

Tissue Expression ◽

Health Concern ◽

Pharmacological Intervention ◽

Peroxisome Proliferator ◽

Expression Of Genes ◽

Ppar Agonists ◽

Prevalence Of Obesity ◽

Peroxisome Proliferator Activated Receptors ◽

Natural And Synthetic

: Obesity is a major health concern for a growing fraction of the population, with the prevalence of obesity and its related metabolic disorders not being fully understood. Over the last decade, many attempts have been undertaken to understand the mechanisms at the basis of this condition, in which the accumulation of fat occurring in adipose tissue, leads to the pathogenesis of obesity related disorders. Among the most recent studies, those on Peroxisome Proliferator Activated Receptors (PPARs) revealed that these nuclear receptor proteins acting as transcription factors, among others, regulate the expression of genes involved in energy, lipid, and glucose metabolisms, and chronic inflammation. The three different isotypes of PPARs, with different tissue expression and ligand binding specificity, exert similar or overlapping functions directly or indirectly linked to obesity. In this study, we reviewed the available scientific reports concerning the PPARs structure and functions, especially in obesity, considering both natural and synthetic ligands and their role in the therapy of obesity and obesity-associated disorders. In the whole, the collected data show that there are both natural and synthetic compounds that show beneficial promising activity as PPAR agonists in chronic diseases related to obesity.

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MULTIPLE ALLELE APPROACH TO THE STUDY OF GENES IN DROSOPHILA MELANOGASTER THAT ARE INVOLVED IN IMAGINAL DISC DEVELOPMENT

Genetics ◽

10.1093/genetics/89.2.355 ◽

1978 ◽

Vol 89 (2) ◽

pp. 355-370 ◽

Cited By ~ 2

Author(s):

Allen Shearn ◽

Grafton Hersperger ◽

Evelyn Hersperger ◽

Ellen Steward Pentz ◽

Paul Denker

Keyword(s):

Drosophila Melanogaster ◽

Phenotypic Variation ◽

Mutant Allele ◽

Imaginal Disc ◽

Reference Allele ◽

Multiple Allele ◽

Significant Difference ◽

Chromosome Mutations ◽

Cold Sensitive

ABSTRACT The phenotypes of five different lethal mutants of Drosophila melanogaster that have small imaginal discs were analyzed in detail. From these results, we inferred whether or not the observed imaginal disc phenotype resulted exclusively from a primary imaginal disc defect in each mutant. To examine the validity of these inferences, we employed a multiple-allele method. Lethal alleles of the five third-chromosome mutations were identified by screening EMS-treated chromosomes for those which fail to complement with a chromosome containing all five reference mutations. Twenty-four mutants were isolated from 13,197 treated chromosomes. Each of the 24 was then tested for complementation with each of the five reference mutants. There was no significant difference in the mutation frequencies at these five loci. The stage of lethality and the imaginal disc morphology of each mutant allele were compared to those of its reference allele in order to examine the range of defects to be found among lethal alleles of each locus. In addition, hybrids of the alleles were examined for intracistronic complementation. For two of the five loci, we detected no significant phenotypic variation among lethal alleles. We infer that each of the mutant alleles at these two loci cause expression of the null activity phenotype. However, for the three other loci, we did detect significant phenotypic variation among lethal alleles. In fact, one of the mutant alleles at each of these three loci causes no detectable imaginal disc defect. This demonstrates that attempting to assess the developmental role of a gene by studying a single mutant allele may lead to erroneous conclusions. As a byproduct of the mutagenesis procedure, we have isolated two dominant, cold-sensitive mutants.

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The Role of Extracellular Vesicles as Shuttles of RNA and Their Clinical Significance as Biomarkers in Hepatocellular Carcinoma

Genes ◽

10.3390/genes12060902 ◽

2021 ◽

Vol 12 (6) ◽

pp. 902

Author(s):

Eva Costanzi ◽

Carolina Simioni ◽

Gabriele Varano ◽

Cinzia Brenna ◽

Ilaria Conti ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Extracellular Vesicles ◽

Tumor Metastasis ◽

Biological Processes ◽

Rna Molecules ◽

Expression Of Genes ◽

Non Coding Rna ◽

Donor Cells ◽

Relevant Role

Extracellular vesicles (EVs) have attracted interest as mediators of intercellular communication following the discovery that EVs contain RNA molecules, including non-coding RNA (ncRNA). Growing evidence for the enrichment of peculiar RNA species in specific EV subtypes has been demonstrated. ncRNAs, transferred from donor cells to recipient cells, confer to EVs the feature to regulate the expression of genes involved in differentiation, proliferation, apoptosis, and other biological processes. These multiple actions require accuracy in the isolation of RNA content from EVs and the methodologies used play a relevant role. In liver, EVs play a crucial role in regulating cell–cell communications and several pathophysiological events in the heterogeneous liver class of cells via horizontal transfer of their cargo. This review aims to discuss the rising role of EVs and their ncRNAs content in regulating specific aspects of hepatocellular carcinoma development, including tumorigenesis, angiogenesis, and tumor metastasis. We analyze the progress in EV-ncRNAs’ potential clinical applications as important diagnostic and prognostic biomarkers for liver conditions.

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Myeloid HIF1α Is Involved in the Extent of Orthodontically Induced Tooth Movement

Biomedicines ◽

10.3390/biomedicines9070796 ◽

2021 ◽

Vol 9 (7) ◽

pp. 796

Author(s):

Christian Kirschneck ◽

Nadine Straßmair ◽

Fabian Cieplik ◽

Eva Paddenberg ◽

Jonathan Jantsch ◽

...

Keyword(s):

Bone Density ◽

Periodontal Ligament ◽

Tooth Movement ◽

Hypoxia Inducible Factor ◽

Myeloid Cells ◽

Orthodontic Tooth Movement ◽

Periodontal Ligament Fibroblasts ◽

Expression Of Genes ◽

Periodontal Bone Loss

During orthodontic tooth movement, transcription factor hypoxia-inducible factor 1α (HIF1α) is stabilised in the periodontal ligament. While HIF1α in periodontal ligament fibroblasts can be stabilised by mechanical compression, in macrophages pressure application alone is not sufficient to stabilise HIF1α. The present study was conducted to investigate the role of myeloid HIF1α during orthodontic tooth movement. Orthodontic tooth movement was performed in wildtype and Hif1αΔmyel mice lacking HIF1α expression in myeloid cells. Subsequently, µCT images were obtained to determine periodontal bone loss, extent of orthodontic tooth movement and bone density. RNA was isolated from the periodontal ligament of the control side and the orthodontically treated side, and the expression of genes involved in bone remodelling was investigated. The extent of tooth movement was increased in Hif1αΔmyel mice. This may be due to the lower bone density of the Hif1αΔmyel mice. Deletion of myeloid Hif1α was associated with increased expression of Ctsk and Acp5, while both Rankl and its decoy receptor Opg were increased. HIF1α from myeloid cells thus appears to play a regulatory role in orthodontic tooth movement.

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HbxB Is a Key Regulator for Stress Response and β-Glucan Biogenesis in Aspergillus nidulans

Microorganisms ◽

10.3390/microorganisms9010144 ◽

2021 ◽

Vol 9 (1) ◽

pp. 144

Author(s):

Sung-Hun Son ◽

Mi-Kyung Lee ◽

Ye-Eun Son ◽

Hee-Soo Park

Keyword(s):

Transcription Factor ◽

Transcription Factors ◽

Aspergillus Nidulans ◽

Deletion Mutant ◽

Phenotypic Analysis ◽

Spore Viability ◽

Fungal Development ◽

Expression Of Genes ◽

Trehalose Biosynthesis

Homeobox transcription factors are conserved in eukaryotes and act as multi-functional transcription factors in filamentous fungi. Previously, it was demonstrated that HbxB governs fungal development and spore viability in Aspergillus nidulans. Here, the role of HbxB in A. nidulans was further characterized. RNA-sequencing revealed that HbxB affects the transcriptomic levels of genes associated with trehalose biosynthesis and response to thermal, oxidative, and radiation stresses in asexual spores called conidia. A phenotypic analysis found that hbxB deletion mutant conidia were more sensitive to ultraviolet stress. The loss of hbxB increased the mRNA expression of genes associated with β-glucan degradation and decreased the amount of β-glucan in conidia. In addition, hbxB deletion affected the expression of the sterigmatocystin gene cluster and the amount of sterigmatocystin. Overall, these results indicated that HbxB is a key transcription factor regulating trehalose biosynthesis, stress tolerance, β-glucan degradation, and sterigmatocystin production in A.nidulans conidia.

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Foam Cells as Therapeutic Targets in Atherosclerosis with a Focus on the Regulatory Roles of Non-Coding RNAs

International Journal of Molecular Sciences ◽

10.3390/ijms22052529 ◽

2021 ◽

Vol 22 (5) ◽

pp. 2529

Author(s):

Amin Javadifar ◽

Sahar Rastgoo ◽

Maciej Banach ◽

Tannaz Jamialahmadi ◽

Thomas P. Johnston ◽

...

Keyword(s):

Lipid Metabolism ◽

Foam Cell ◽

Cell Formation ◽

Foam Cells ◽

Foam Cell Formation ◽

Special Focus ◽

Lipid Uptake ◽

Therapeutic Goals ◽

Expression Of Genes

Atherosclerosis is a major cause of human cardiovascular disease, which is the leading cause of mortality around the world. Various physiological and pathological processes are involved, including chronic inflammation, dysregulation of lipid metabolism, development of an environment characterized by oxidative stress and improper immune responses. Accordingly, the expansion of novel targets for the treatment of atherosclerosis is necessary. In this study, we focus on the role of foam cells in the development of atherosclerosis. The specific therapeutic goals associated with each stage in the formation of foam cells and the development of atherosclerosis will be considered. Processing and metabolism of cholesterol in the macrophage is one of the main steps in foam cell formation. Cholesterol processing involves lipid uptake, cholesterol esterification and cholesterol efflux, which ultimately leads to cholesterol equilibrium in the macrophage. Recently, many preclinical studies have appeared concerning the role of non-encoding RNAs in the formation of atherosclerotic lesions. Non-encoding RNAs, especially microRNAs, are considered regulators of lipid metabolism by affecting the expression of genes involved in the uptake (e.g., CD36 and LOX1) esterification (ACAT1) and efflux (ABCA1, ABCG1) of cholesterol. They are also able to regulate inflammatory pathways, produce cytokines and mediate foam cell apoptosis. We have reviewed important preclinical evidence of their therapeutic targeting in atherosclerosis, with a special focus on foam cell formation.

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Non-alcoholic fatty liver disease in mice with hepatocyte-specific deletion of mitochondrial fission factor

Diabetologia ◽

10.1007/s00125-021-05488-2 ◽

2021 ◽

Author(s):

Yukina Takeichi ◽

Takashi Miyazawa ◽

Shohei Sakamoto ◽

Yuki Hanada ◽

Lixiang Wang ◽

...

Keyword(s):

Er Stress ◽

Mitochondrial Dynamics ◽

Mitochondrial Fission ◽

Primary Hepatocytes ◽

Alcoholic Fatty Liver ◽

Expression Of Genes ◽

Specific Deletion

Abstract Aims/hypothesis Mitochondria are highly dynamic organelles continuously undergoing fission and fusion, referred to as mitochondrial dynamics, to adapt to nutritional demands. Evidence suggests that impaired mitochondrial dynamics leads to metabolic abnormalities such as non-alcoholic steatohepatitis (NASH) phenotypes. However, how mitochondrial dynamics are involved in the development of NASH is poorly understood. This study aimed to elucidate the role of mitochondrial fission factor (MFF) in the development of NASH. Methods We created mice with hepatocyte-specific deletion of MFF (MffLiKO). MffLiKO mice fed normal chow diet (NCD) or high-fat diet (HFD) were evaluated for metabolic variables and their livers were examined by histological analysis. To elucidate the mechanism of development of NASH, we examined the expression of genes related to endoplasmic reticulum (ER) stress and lipid metabolism, and the secretion of triacylglycerol (TG) using the liver and primary hepatocytes isolated from MffLiKO and control mice. Results MffLiKO mice showed aberrant mitochondrial morphologies with no obvious NASH phenotypes during NCD, while they developed full-blown NASH phenotypes in response to HFD. Expression of genes related to ER stress was markedly upregulated in the liver from MffLiKO mice. In addition, expression of genes related to hepatic TG secretion was downregulated, with reduced hepatic TG secretion in MffLiKO mice in vivo and in primary cultures of MFF-deficient hepatocytes in vitro. Furthermore, thapsigargin-induced ER stress suppressed TG secretion in primary hepatocytes isolated from control mice. Conclusions/interpretation We demonstrated that ablation of MFF in liver provoked ER stress and reduced hepatic TG secretion in vivo and in vitro. Moreover, MffLiKO mice were more susceptible to HFD-induced NASH phenotype than control mice, partly because of ER stress-induced apoptosis of hepatocytes and suppression of TG secretion from hepatocytes. This study provides evidence for the role of mitochondrial fission in the development of NASH. Graphical abstract

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Dietary starch promotes hepatic lipogenesis in barramundi (Lates calcarifer)

British Journal Of Nutrition ◽

10.1017/s0007114520001051 ◽

2020 ◽

Vol 124 (4) ◽

pp. 363-373

Author(s):

N. M. Wade ◽

L. H. Trenkner ◽

I. Viegas ◽

L. C. Tavares ◽

M. Palma ◽

...

Keyword(s):

Mammalian Target Of Rapamycin ◽

Sea Bass ◽

Metabolic Effects ◽

Lates Calcarifer ◽

Glucose Levels ◽

H Nmr ◽

Expression Of Genes ◽

Fractional Synthetic Rate ◽

Dietary Starch

AbstractBarramundi (Lates calcarifer) are a highly valued aquaculture species, and, as obligate carnivores, they have a demonstrated preference for dietary protein over lipid or starch to fuel energetic growth demands. In order to investigate how carnivorous fish regulate nutritional cues, we examined the metabolic effects of feeding two isoenergetic diets that contained different proportions of digestible protein or starch energy. Fish fed a high proportion of dietary starch energy had a higher proportion of liver SFA, but showed no change in plasma glucose levels, and few changes in the expression of genes regulating key hepatic metabolic pathways. Decreased activation of the mammalian target of rapamycin growth signalling cascade was consistent with decreased growth performance values. The fractional synthetic rate (lipogenesis), measured by TAG 2H-enrichment using 2H NMR, was significantly higher in barramundi fed with the starch diet compared with the protein diet (0·6 (se 0·1) v. 0·4 (se 0·1) % per d, respectively). Hepatic TAG-bound glycerol synthetic rates were much higher than other closely related fish such as sea bass, but were not significantly different (starch, 2·8 (se 0·3) v. protein, 3·4 (se 0·3) % per d), highlighting the role of glycerol as a metabolic intermediary and high TAG-FA cycling in barramundi. Overall, dietary starch significantly increased hepatic TAG through increased lipogenesis. Compared with other fish, barramundi possess a unique mechanism to metabolise dietary carbohydrates and this knowledge may define ways to improve performance of advanced formulated feeds.

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