scholarly journals The tissue specific regulation of miR22 expression in the lung and brain by ribosomal protein L29

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Mohammad Ishaque Ali ◽  
Linrui Li ◽  
Lexing Li ◽  
Lun Yao ◽  
Jie Liu ◽  
...  
Keyword(s):  
Inhibitory Effect ◽  
Poly I:C ◽  
Mouse Lung ◽  
Biological Processes ◽  
Post Translational Modification ◽  
Negative Effects ◽  
Specific Expression ◽  
Diverse Range ◽  
Cell Specificity ◽  
Specific Regulation

Abstract Endogenous miR22 is associated with a diverse range of biological processes through post-translational modification of gene expression and its deregulation results in various diseases including cancer. Its expression is usually tissue or cell-specific, however, the reasons behind this tissue or cell specificity are not clearly outlined till-date. Therefore, our keen interest was to investigate the mechanisms of tissue or cell-specific expression of miR22. In the current study, miR22 expression showed a tissues-specific difference in the poly(I:C) induced inflammatory mouse lung and brain tissues. The cell-specific different expression of miR22 was also observed in inflammatory glial cells and endothelial cells. The pattern of RPL29 expression was also similar to miR22 in these tissues and cells under the same treatment. Interestingly, the knockdown of RPL29 exerted an inhibitory effect on miR22 and its known transcription factors including Fos-B and c-Fos. Fos-B and c-Fos were also differentially expressed in the two cell lines transfected with poly(I:C). The knockdown of c-Fos also exerted its negative effects on miR22 expression in both cells. These findings suggest that RPL29 might have regulatory roles on tissue or cell-specific expression of miR22 through the transcription activities of c-Fos and also possibly through Fos-B.

Review of Progress in Predicting Protein Methylation Sites

2019 ◽  
Vol 23 (15) ◽  
pp. 1663-1670 ◽  
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.

scholarly journals PRV UL13 inhibits cGAS–STING-mediated IFN-β production by phosphorylating IRF3

2020 ◽  
Vol 51 (1) ◽  
Author(s):  
Zongyi Bo ◽  
Yurun Miao ◽  
Rui Xi ◽  
Qiuping Zhong ◽  
Chenyi Bao ◽  
...  
Keyword(s):  
Transcriptional Activation ◽  
Pseudorabies Virus ◽  
Nuclear Translocation ◽  
Economic Loss ◽  
Inhibitory Effect ◽  
Poly I:C ◽  
Interferon Response ◽  
Type I ◽  
Creb Binding Protein ◽  
Swine Industry

Abstract Cyclic GMP-AMP (cGAMP) synthase (cGAS) is an intracellular sensor of cytoplasmic viral DNA created during virus infection, which subsequently activates the stimulator of interferon gene (STING)-dependent type I interferon response to eliminate pathogens. In contrast, viruses have developed different strategies to modulate this signalling pathway. Pseudorabies virus (PRV), an alphaherpesvirus, is the causative agent of Aujeszky’s disease (AD), a notable disease that causes substantial economic loss to the swine industry globally. Previous reports have shown that PRV infection induces cGAS-dependent IFN-β production, conversely hydrolysing cGAMP, a second messenger synthesized by cGAS, and attenuates PRV-induced IRF3 activation and IFN-β secretion. However, it is not clear whether PRV open reading frames (ORFs) modulate the cGAS–STING-IRF3 pathway. Here, 50 PRV ORFs were screened, showing that PRV UL13 serine/threonine kinase blocks the cGAS–STING-IRF3-, poly(I:C)- or VSV-mediated transcriptional activation of the IFN-β gene. Importantly, it was discovered that UL13 phosphorylates IRF3, and its kinase activity is indispensable for such an inhibitory effect. Moreover, UL13 does not affect IRF3 dimerization, nuclear translocation or association with CREB-binding protein (CBP) but attenuates the binding of IRF3 to the IRF3-responsive promoter. Consistent with this, it was discovered that UL13 inhibits the expression of multiple interferon-stimulated genes (ISGs) induced by cGAS–STING or poly(I:C). Finally, it was determined that PRV infection can activate IRF3 by recruiting it to the nucleus, and PRVΔUL13 mutants enhance the transactivation level of the IFN-β gene. Taken together, the data from the present study demonstrated that PRV UL13 inhibits cGAS–STING-mediated IFN-β production by phosphorylating IRF3.

scholarly journals Targeting the Ubiquitin Signaling Cascade in Tumor Microenvironment for Cancer Therapy

2021 ◽  
Vol 22 (2) ◽  
pp. 791
Author(s):  
Qi Liu ◽  
Bayonle Aminu ◽  
Olivia Roscow ◽  
Wei Zhang
Keyword(s):  
Tumor Microenvironment ◽  
Cancer Therapy ◽  
Therapeutic Agents ◽  
Biological Processes ◽  
Post Translational Modification ◽  
E3 Ligases ◽  
Tumor Microenvironments ◽  
Cellular Immune ◽  
Ubiquitin Conjugating Enzymes ◽  
Cellular Components

Tumor microenvironments are composed of a myriad of elements, both cellular (immune cells, cancer-associated fibroblasts, mesenchymal stem cells, etc.) and non-cellular (extracellular matrix, cytokines, growth factors, etc.), which collectively provide a permissive environment enabling tumor progression. In this review, we focused on the regulation of tumor microenvironment through ubiquitination. Ubiquitination is a reversible protein post-translational modification that regulates various key biological processes, whereby ubiquitin is attached to substrates through a catalytic cascade coordinated by multiple enzymes, including E1 ubiquitin-activating enzymes, E2 ubiquitin-conjugating enzymes and E3 ubiquitin ligases. In contrast, ubiquitin can be removed by deubiquitinases in the process of deubiquitination. Here, we discuss the roles of E3 ligases and deubiquitinases as modulators of both cellular and non-cellular components in tumor microenvironment, providing potential therapeutic targets for cancer therapy. Finally, we introduced several emerging technologies that can be utilized to develop effective therapeutic agents for targeting tumor microenvironment.

scholarly journals The AGA1 product is involved in cell surface attachment of the Saccharomyces cerevisiae cell adhesion glycoprotein a-agglutinin.

1991 ◽  
Vol 11 (8) ◽  
pp. 4196-4206 ◽  
Author(s):  
A Roy ◽  
C F Lu ◽  
D L Marykwas ◽  
P N Lipke ◽  
J Kurjan
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Cell Surface ◽  
Signal Sequence ◽  
Complementation Group ◽  
Alpha Cells ◽  
Specific Expression ◽  
Surface Attachment ◽  
Cellular Aggregation ◽  
Specific Regulation ◽  
Binding Subunit

Saccharomyces cerevisiae a and alpha cells express the complementary cell surface glycoproteins a-agglutinin and alpha-agglutinin, respectively, which interact with one another to promote cellular aggregation during mating. Treatment of S. cerevisiae a cells with reducing agents releases the binding subunit of a-agglutinin, which has been purified and characterized; little biochemical information on the overall structure of a-agglutinin is available. To characterise a-agglutinin structure and function, we have used a genetic approach to clone an a-agglutinin structural gene (AGAI). Mutants with a-specific agglutination defects were isolated, the majority of which fell into a single complementation group, called aga1. The aga1 mutants showed wild-type pheromone production and response, efficient mating on solid medium, and a mating defect in liquid medium; these phenotypes are characteristic of agglutinin mutants. The AGA1 gene was cloned by complementation; the gene sequence indicated that it could encode a protein of 725 amino acids with high serine and threonine content, a putative N-terminal signal sequence, and a C-terminal hydrophobic sequence similar to signals for the attachment to glycosyl phosphatidylinositol anchors. Active a-agglutinin binding subunit is secreted by aga1 mutants, indicating that AGA1 is involved in cells surface attachment of a-agglutinin. This result suggests that AGA1 encodes a protein with functional similarity to the core subunits of a-agglutinin analogs from other budding yeasts. Unexpectedly, the AGA1 transcript was expressed and induced by pheromone in both a and alpha cells, suggesting that the a-specific expression of active a-agglutinin results only from a-specific regulation of the a-agglutinin binding subunit.

Cellular promoters incorporated into the adenovirus genome: effects of viral regulatory elements on transcription rates and cell specificity of albumin and beta-globin promoters

1986 ◽  
Vol 6 (11) ◽  
pp. 3798-3806
Author(s):  
L E Babiss ◽  
J M Friedman ◽  
J E Darnell
Keyword(s):  
Cultured Cells ◽  
Regulatory Elements ◽  
Beta Globin ◽  
Specific Expression ◽  
Adenovirus E1a ◽  
Differentiated Cells ◽  
Cell Specificity ◽  
293 Cells ◽  
Specific Factors ◽  
Globin Promoter

In the accompanying paper (Friedman et al., Mol. Cell. Biol. 6:3791-3797, 1986), hepatoma-specific expression of the rat albumin promoter within the adenovirus genome was demonstrated. However, the rate of transcription was very low compared with that of the endogenous chromosomal albumin gene. Here we show that in hepatoma cells the adenovirus E1A enhancer, especially in the presence of E1A protein, greatly stimulates transcription from the albumin promoter but not the mouse beta-globin promoter. This enhancer-dependent stimulation did not occur in myeloma cells in which a virus containing a immunoglobulin promoter and enhancer did function. These experiments suggest a limited distribution in cultured differentiated cells of cell-specific transcription factors. However, either the regulation of such cell-specific factors breaks down in other cultured cells, or strictly cell-specific factors are not at play in controlling cell-specific transcription, because HeLa cells could transcribe the albumin promoter from the same start site about 10% as well as hepatomas could and 293 cells could transcribe both albumin and globin promoters.

Calcitonin/calcitonin gene-related peptide transcription unit: tissue-specific expression involves selective use of alternative polyadenylation sites

1984 ◽  
Vol 4 (10) ◽  
pp. 2151-2160
Author(s):  
S G Amara ◽  
R M Evans ◽  
M G Rosenfeld
Keyword(s):  
Regulation Of Gene Expression ◽  
Alternative Polyadenylation ◽  
Calcitonin Gene Related Peptide ◽  
Transcription Unit ◽  
Specific Expression ◽  
Tissue Specific ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Polyadenylation Sites ◽  
Specific Regulation

Different 3' coding exons in the rat calcitonin gene are used to generate distinct mRNAs encoding either the hormone calcitonin in thyroidal C-cells or a new neuropeptide referred to as calcitonin gene-related peptide in neuronal tissue, indicating the RNA processing regulation is one strategy used in tissue-specific regulation of gene expression in the brain. Although the two mRNAs use the same transcriptional initiation site and have identical 5' terminal sequences, their 3' termini are distinct. The polyadenylation sites for calcitonin and calcitonin gene-related peptide mRNAs are located at the end of the exons 4 and 6, respectively. Termination of transcription after the calcitonin exon does not dictate the production of calcitonin mRNA, because transcription proceeds through both calcitonin and calcitonin gene-related peptide exons irrespective of which mRNA is ultimately produced. In isolated nuclei, both polyadenylation sites appear to be utilized; however, the proximal (calcitonin) site is preferentially used in nuclei from tissues producing calcitonin mRNA. These data suggest that the mechanism dictating production of each mRNA involves the selective use of alternative polyadenylation sites.

Overlapping positive and negative regulatory elements determine lens-specific activity of the delta 1-crystallin enhancer

1993 ◽  
Vol 13 (9) ◽  
pp. 5206-5215 ◽  
Author(s):  
Y Kamachi ◽  
H Kondoh
Keyword(s):  
Mutational Analysis ◽  
Specific Activity ◽  
Regulatory Elements ◽  
Positive Element ◽  
Specific Expression ◽  
Enhancer Activity ◽  
Negative Element ◽  
Positive Elements ◽  
Lens Cells ◽  
Specific Regulation

Lens-specific expression of the delta 1-crystallin gene is governed by an enhancer in the third intron, and the 30-bp-long DC5 fragment was found to be responsible for eliciting the lens-specific activity. Mutational analysis of the DC5 fragment identified two contiguous, interdependent positive elements and a negative element which overlaps the 3'-located positive element. Previously identified ubiquitous factors delta EF1 bound to the negative element and repressed the enhancer activity in nonlens cells. Mutation and cotransfection analyses indicated the existence of an activator which counteracts the action of delta EF1 in lens cells, probably through binding site competition. We also found a group of nuclear factors, collectively called delta EF2, which bound to the 5'-located positive element. delta EF2a and -b were the major species in lens cells, whereas delta EF2c and -d predominated in nonlens cells. These delta EF2 proteins probably cooperate with factors bound to the 3'-located element in activation in lens cells and repression in nonlens cells. delta EF2 proteins also bound to a promoter sequence of the gamma F-crystallin gene, suggesting that delta EF2 proteins are involved in lens-specific regulation of various crystallin classes.

scholarly journals Promoter-specific regulation of PPARGC1A gene expression in human skeletal muscle

2015 ◽  
Vol 55 (2) ◽  
pp. 159-168 ◽  
Author(s):  
Daniil V Popov ◽  
Evgeny A Lysenko ◽  
Tatiana F Vepkhvadze ◽  
Nadia S Kurochkina ◽  
Pavel A Maknovskii ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Human Skeletal Muscle ◽  
Stop Codon ◽  
Constitutive Expression ◽  
Alternative Promoter ◽  
Specific Expression ◽  
Post Exercise ◽  
Specific Regulation ◽  
Intensity Of Exercise

The goal of this study was to identify unknown transcription start sites of thePPARGC1A(PGC-1α) gene in human skeletal muscle and investigate the promoter-specific regulation ofPGC-1αgene expression in human skeletal muscle. Ten amateur endurance-trained athletes performed high- and low-intensity exercise sessions (70 min, 70% or 50%o2max). High-throughput RNA sequencing and exon–exon junction mapping were applied to analyse muscle samples obtained at rest and after exercise.PGC-1αpromoter-specific expression and activation of regulators of PGC-1α gene expression (AMPK, p38 MAPK, CaMKII, PKA and CREB1) after exercise were evaluated using qPCR and western blot. Our study has demonstrated that during post-exercise recovery, human skeletal muscle expresses thePGC-1αgene via two promoters only. As previously described, the additional exon 7a that contains a stop codon was found in all samples. Importantly, only minor levels of other splice site variants were found (and not in all samples). Constitutive expressionPGC-1αgene occurs via the canonical promoter, independent of exercise intensity and exercise-induced increase of AMPKThr172phosphorylation level. Expression ofPGC-1αgene via the alternative promoter is increased of two orders after exercise. This post-exercise expression is highly dependent on the intensity of exercise. There is an apparent association between expression via the alternative promoter and activation of CREB1.

Understanding cellular glycan surfaces in the central nervous system

2018 ◽  
Vol 47 (1) ◽  
pp. 89-100 ◽  
Author(s):  
Sameera Iqbal ◽  
Mina Ghanimi Fard ◽  
Arun Everest-Dass ◽  
Nicolle H. Packer ◽  
Lindsay M. Parker
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Neural Development ◽  
Analytical Techniques ◽  
Detection Methods ◽  
Biological Processes ◽  
Post Translational Modification ◽  
Enzymatic Process ◽  
The Central Nervous System ◽  
Lateral Sclerosis

Abstract Glycosylation, the enzymatic process by which glycans are attached to proteins and lipids, is the most abundant and functionally important type of post-translational modification associated with brain development, neurodegenerative disorders, psychopathologies and brain cancers. Glycan structures are diverse and complex; however, they have been detected and targeted in the central nervous system (CNS) by various immunohistochemical detection methods using glycan-binding proteins such as anti-glycan antibodies or lectins and/or characterized with analytical techniques such as chromatography and mass spectrometry. The glycan structures on glycoproteins and glycolipids expressed in neural stem cells play key roles in neural development, biological processes and CNS maintenance, such as cell adhesion, signal transduction, molecular trafficking and differentiation. This brief review will highlight some of the important findings on differential glycan expression across stages of CNS cell differentiation and in pathological disorders and diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease, multiple sclerosis, amyotrophic lateral sclerosis, schizophrenia and brain cancer.

scholarly journals Effectiveness of Three Post-Harvest Rehabilitation Treatments for Runoff and Sediment Reduction on Skid Trails in the Hyrcanian Forests

2020 ◽  
Vol 41 (2) ◽  
pp. 309-324
Author(s):  
Meghdad Jourgholami ◽  
Masoumeh Ahmadi ◽  
Farzam Tavankar ◽  
Rodolfo Picchio
Keyword(s):  
Leaf Litter ◽  
Sediment Yield ◽  
Rainfall Intensity ◽  
Regression Equations ◽  
Negative Effects ◽  
Diverse Range ◽  
Straw Mulch ◽  
The Impact ◽  
Different Levels ◽  
Runoff And Sediment Yield

Ground-based skidding operations can lead to soil compaction and displacement, which could cause negative effects on forest soil. Hence, some efforts such as forestry best management practices (BMPs) must be implemented in the prone area to mitigate these possible impacts. Several materials and treatments have been adopted to suppress these adverse effects by increasing the ground cover. However, the effects of mulch treatments on runoff and sediment yield are inconclusive with a diverse range of effectiveness. For these reasons, in this research mulch treatments were tested as to determine how the application of organic mulch amendments such as straw and leaf litter and contour-felled logs would alleviate the runoff and sediment yield on machine operating trails and ensure successful hillslope stabilization. The aims of the study were to analyse and compare the effectiveness of leaf litter (LM) and straw mulch (SM) rate and different distances of contour-felled logs (CFL) to mitigate the runoff and sediment yield, and examine the impact of rainfall intensity on effectiveness of litter mulch, straw mulch, and contour-felled logs. Totally, 30 bounded runoff plots in the machine operating trails and four treatments including litter mulch (LMR1: 0.62, LMR2: 1.24, and LMR3: 1.86 kg m-2), straw mulch (SMR1: 0.45, SMR2: 0.92, and SMR3: 1.34 kg m-2), contour-felled logs (CFL10: 10, CFL20: 20, and CFL30: 30 m), and untreated area were established in triplicate with 4 m width and 100 m length. During the study period, the runoff and sediment yield in the untreated trails (U) were 2.36 mm and 11.84 g m-2. Straw (from 41.5 to 60.6%) and litter mulch (from 38.1 to 55.1%), and contour-felled logs treatments (from 70.8 to 88.1%) significantly decreased the runoff, compared to U treatment. Results show that mulch treatments with three different levels of Litter Mulch Rate, LMR1, LMR2, and LMR3 decreased mean sediment by 46.6, 64.0 and 71.8%, in the treatments with three different levels of Straw Mulch Rate, SMR1, SMR2, and SMR3 decreased mean sediment by 42.9, 62.1, and 69.9%, and in the treatments with three different distances of Contour-Felled Logs, CFL10, CFL20, and CFL30 decreased mean sediment by 90.6, 94.7 and 88.3% comparing to U, respectively. The relationships of the runoff and sediment responses to increasing mulching rate of litter and straw followed as negative logarithmic curves, but the decreasing-increasing trends were observed in runoff and sediment yield as the distance between contour-felled logs increased from 10 to 30 m. Polynomial regression equations were developed for predicting the runoff and sediment yield as a function of the application rate of litter and straw mulch and the distance between contour-felled logs, and rainfall intensity. We concluded that contour-felled logs treatment was more effective than both litter and straw mulch to mitigate the runoff, runoff coefficient, and sediment yield on machine operating trails. As a management measure, it could be possible to propose that the contour-felled logs with a distance of 20 m be prescribed to protect the machine operating trails from the negative effects of surface waterflow.

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