scholarly journals Sensory Neuropathy Affects Cardiac miRNA Expression Network Targeting IGF-1, SLC2a-12, EIF-4e, and ULK-2 mRNAs

2019 ◽  
Vol 20 (4) ◽  
pp. 991 ◽  
Author(s):  
Péter Bencsik ◽  
Krisztina Kiss ◽  
Bence Ágg ◽  
Júlia Baán ◽  
Gergely Ágoston ◽  
...  
Keyword(s):  
Diastolic Dysfunction ◽  
Mirna Expression ◽  
In Silico ◽  
Glucose Transporter ◽  
Molecular Targets ◽  
Sensory Neuropathy ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Qrt Pcr ◽  
Mrna Targets

Background: Here we examined myocardial microRNA (miRNA) expression profile in a sensory neuropathy model with cardiac diastolic dysfunction and aimed to identify key mRNA molecular targets of the differentially expressed miRNAs that may contribute to cardiac dysfunction. Methods: Male Wistar rats were treated with vehicle or capsaicin for 3 days to induce systemic sensory neuropathy. Seven days later, diastolic dysfunction was detected by echocardiography, and miRNAs were isolated from the whole ventricles. Results: Out of 711 known miRNAs measured by miRNA microarray, the expression of 257 miRNAs was detected in the heart. As compared to vehicle-treated hearts, miR-344b, miR-466b, miR-98, let-7a, miR-1, miR-206, and miR-34b were downregulated, while miR-181a was upregulated as validated also by quantitative real time polymerase chain reaction (qRT-PCR). By an in silico network analysis, we identified common mRNA targets (insulin-like growth factor 1 (IGF-1), solute carrier family 2 facilitated glucose transporter member 12 (SLC2a-12), eukaryotic translation initiation factor 4e (EIF-4e), and Unc-51 like autophagy activating kinase 2 (ULK-2)) targeted by at least three altered miRNAs. Predicted upregulation of these mRNA targets were validated by qRT-PCR. Conclusion: This is the first demonstration that sensory neuropathy affects cardiac miRNA expression network targeting IGF-1, SLC2a-12, EIF-4e, and ULK-2, which may contribute to cardiac diastolic dysfunction. These results further support the need for unbiased omics approach followed by in silico prediction and validation of molecular targets to reveal novel pathomechanisms.

scholarly journals In silico analysis of bacterial translation factors reveal distinct translation event specific pI values

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Soma Jana ◽  
Partha P. Datta
Keyword(s):  
Translation Initiation ◽  
In Silico ◽  
Bacterial Species ◽  
Amino Acid Sequences ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Release Factors ◽  
Translation Factors ◽  
70S Ribosome ◽  
Bacterial Translation

Abstract Background Protein synthesis is a cellular process that takes place through the successive translation events within the ribosome by the event-specific protein factors, namely, initiation, elongation, release, and recycling factors. In this regard, we asked the question about how similar are those translation factors to each other from a wide variety of bacteria? Hence, we did a thorough in silico study of the translation factors from 495 bacterial sp., and 4262 amino acid sequences by theoretically measuring their pI and MW values that are two determining factors for distinguishing individual proteins in 2D gel electrophoresis in experimental procedures. Then we analyzed the output from various angles. Results Our study revealed the fact that it’s not all same, or all random, but there are distinct orders and the pI values of translation factors are translation event specific. We found that the translation initiation factors are mainly basic, whereas, elongation and release factors that interact with the inter-subunit space of the intact 70S ribosome during translation are strictly acidic across bacterial sp. These acidic elongation factors and release factors contain higher frequencies of glutamic acids. However, among all the translation factors, the translation initiation factor 2 (IF2) and ribosome recycling factor (RRF) showed variable pI values that are linked to the order of phylogeny. Conclusions From the results of our study, we conclude that among all the bacterial translation factors, elongation and release factors are more conserved in terms of their pI values in comparison to initiation and recycling factors. Acidic properties of these factors are independent of habitat, nature, and phylogeny of the bacterial species. Furthermore, irrespective of the different shapes, sizes, and functions of the elongation and release factors, possession of the strictly acidic pI values of these translation factors all over the domain Bacteria indicates that the acidic nature of these factors is a necessary criterion, perhaps to interact into the partially enclosed rRNA rich inter-subunit space of the translating 70S ribosome.

scholarly journals In silico analysis of bacterial translation factors reveal distinct translation event specific pI values

2020 ◽  
Author(s):  
SOMA JANA ◽  
Partha Pratim Datta
Keyword(s):  
Translation Initiation ◽  
In Silico ◽  
Bacterial Species ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Acidic Property ◽  
Release Factors ◽  
Translation Factors ◽  
70S Ribosome ◽  
Bacterial Translation

Abstract Background Protein synthesis is a cellular process that takes place through the successive translation events within the ribosome with the help of the event-specific protein factors, namely, initiation, elongation, release, and recycling factors. The translation process is fundamental to all organisms living in the wide variety of environments. In this regard, we asked the questions about how similar are those translation factors to each other from a wide variety of bacteria? Hence, we did a thorough in silico study of the translation factors from 495 bacterial sp., and 4262 amino acid sequences, wherein we theoretically measured their pI and MW values that are the two determining factors for distinguishing individual proteins in 2D gel electrophoresis. Then we analyzed the output from various angles. Results Our study revealed that, not all the pI values are same or random, but there is a distinct order, such that the pI values of translation factors are translation event specific. We found that the translation initiation factors are mainly basic, whereas, elongation and release factors that interact with the inter-subunit space of the intact 70S ribosome during translation are strictly acidic. Further analysis revealed that the acidic property of those factors is due to the higher frequencies of glutamic acids. However, two translation factors, the translation initiation factor 2 (IF2) and the ribosome recycling factor (RRF) showed variable pI values. Remarkably, the variability of the pI values of these two factors showed distinct lineage with the order of phylogeny. Conclusion From our results we conclude that, among all the bacterial translation factors, elongation and release factors are more conserved in terms of their pI values in comparison to initiation and recycling factors. Acidic properties of these factors are independent of habitat, nature, or the phylogeny of the bacterial species. Furthermore; irrespective of the different shapes, sizes, and functions of the elongation and release factors, possession of their strictly acidic pI values indicate that the acidic nature of these factors is a necessary criterion, perhaps to interact into the partially enclosed rRNA rich inter-subunit space of the translating 70S ribosome.

scholarly journals Molecular Structure and Functional Elucidation of IF-3 Protein of Chloroflexus Aurantiacus Involved in Protein Biosynthesis: An In-Silico Approach

2021 ◽  
Author(s):  
Abu Saim Mohammad Saikat
Keyword(s):  
Translation Initiation ◽  
Protein Interactions ◽  
In Silico ◽  
Tertiary Structure ◽  
Protein Biosynthesis ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Chloroflexus Aurantiacus ◽  
Protein Protein Interactions ◽  
Functional Interpretation

<p><i>Chloroflexus aurantiacus</i> is a thermophilic bacterium that produces a multitude of proteins within its genome. Bioinformatics strategies can facilitate comprehending this organism through functional and structural interpretation assessments. This study aimed to allocate the structure and function through an in-silico approach required for bacterial protein biosynthesis. This in-silico viewpoint provides copious properties, including the physicochemical properties, subcellular location, three-dimensional structure, protein-protein interactions, and functional elucidation of the protein (WP_012256288.1). The STRING program is utilized for the explication of protein-protein interactions. The in-silico investigation documented the protein's hydrophilic nature with predominantly alpha (α) helices in its secondary structure. The tertiary-structure model of the protein has been shown to exhibit reasonably high consistency based on various quality assessment methods. The functional interpretation suggested that the protein can act as a translation initiation factor, a protein required for translation and protein biosynthesis. Protein-protein interactions also demonstrated high credence that the protein interconnected with 30S ribosomal subunit involved in protein synthesis. This study is bioinformatically examined that the protein (WP_012256288.1) is affiliated in protein biosynthesis as a translation initiation factor IF-3 of <i>C. aurantiacus</i>. </p> <p> </p>

scholarly journals Structural and Functional Elucidation of IF-3 Protein of Chloroflexus aurantiacus Involved in Protein Biosynthesis: An In-Silico Approach

2021 ◽  
Author(s):  
Abu Saim Mohammad Saikat ◽  
Md. Ekhlas Uddin ◽  
Tasnim Ahmad ◽  
Shahriar Mahmud ◽  
Md. Abu Sayeed Imran ◽  
...  
Keyword(s):  
Translation Initiation ◽  
Protein Interactions ◽  
In Silico ◽  
Tertiary Structure ◽  
Protein Biosynthesis ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Chloroflexus Aurantiacus ◽  
Protein Protein Interactions ◽  
Functional Interpretation

<p>Chloroflexus aurantiacus is a thermophilic bacterium that produces a multitude of proteins<br>within its genome. Bioinformatics strategies can facilitate comprehending this organism through<br>functional and structural interpretation assessments.This study aimed to allocate the structure and<br>function through an in-silico approach required for bacterial protein biosynthesis. This in-silico<br>viewpoint provides copious properties, including the physicochemical properties, subcellular location,<br>three-dimensional structure, protein-protein interactions, and functional elucidation of the protein<br>(WP_012256288.1). The STRING program is utilized for the explication of protein-protein<br>interactions. The in-silico investigation documented the protein's hydrophilic nature with<br>predominantly alpha (α) helices in its secondary structure.The tertiary-structure model of the protein<br>has been shown to exhibit reasonably high consistency based on various quality assessment<br>methods.The functional interpretation suggested that the protein can act as a translation initiation<br>factor, a protein required for translation and protein biosynthesis. Protein-protein interactions also<br>demonstrated high credence that the protein interconnected with 30S ribosomal subunit involved in<br>protein synthesis. This study is bioinformatically examined that the protein (WP_012256288.1) is<br>affiliated in protein biosynthesis as a translation initiation factor IF-3 of C. aurantiacus. <br><br></p>

scholarly journals RNA Sequencing Reveals Novel LncRNAs/mRNAs Network Associated with Puerarin-mediated Inhibition of Cardiac Hypertrophy in Mice

2021 ◽  
Author(s):  
Shan Ye ◽  
Wei-Yang Chen ◽  
Caiwen Ou ◽  
Min-Sheng Chen
Keyword(s):  
Mouse Model ◽  
Cardiac Hypertrophy ◽  
Protective Effect ◽  
Rna Sequencing ◽  
Expression Patterns ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Biological Processes ◽  
Rna Seq ◽  
Qrt Pcr

Abstract Background: Evidence has demonstrated that puerarin is a potential drug for the treatment of cardiac hypertrophy. However, the precise underlying molecular mechanisms of the protective effect of puerarin are still unclear. Here, we aimed to explore the regulatory mechanisms of lncRNAs/mRNAs in a cardiac hypertrophy mouse model after puerarin treatment.Methods: A mouse model of cardiac hypertrophy was established by transverse aortic constriction (TAC). The echocardiography, tissue staining and western blot were used to examine the protective effect of puerarin. Then RNA sequencing (RNA-seq) was carried out to systematically analyze global gene expression. The target lncRNAs were confirmed using qRT-PCR. Moreover, a coding/non-coding gene co-expression (CNC) network was established to find the interaction of lncRNAs and mRNAs. The molecular functions, biological processes, molecular components and pathways of different expression mRNAs targeted by lncRNA were explored using Gene Ontology (GO) analysis and Kyto Encyclopedia of Genes and Genomes (KEGG) pathways analysis.Results: Puerarin exhibited obvious inhibitory effect in cardiac hypertrophy in TAC model. RNA-seq analysis was performed to investigate the lncRNAs and mRNAs expression patterns of cardiomyocytes in sham and TAC groups treated with or without puerarin. RNA-seq identified that TAC upregulated 19 lncRNAs and downregulated 18 lncRNAs, which could be revised by puerarin treatment (Fold change ≥ 3 and P< 0.05). Expression alterations of selected lncRNAs ENSMUST00000125726, ENSMUST00000143044 and ENSMUST00000212795 were confirmed by qRT-PCR. Pearson’s correlation coefficients of co-expression levels suggested that there was interactive relationship between those 3 validated altered lncRNAs and 5,500 mRNAs (r > 0.95 or r < −0.95). Those co-expressed mRNAs were enriched in some important biological processes such as vesicle-mediated transport, sin 3 complex, and translation initiation factor activity. KEGG analyses suggested that those lncRNA-interacted mRNAs were enriched in RNA transport, ribosome biogenesis in eukaryotes and proteasome signaling pathway. Conclusion: Puerarin may exert beneficial effects on cardiac hypertrophy through regulating the ENSMUST00000125726 /ENSMUST00000143044 / ENSMUST00000212795 -mRNAs network.

scholarly journals Comparative Genomic Assessment of Novel Broad-Spectrum Targets for Antibacterial Drugs

2004 ◽  
Vol 5 (4) ◽  
pp. 304-327 ◽  
Author(s):  
Thomas A. White ◽  
Douglas B. Kell
Keyword(s):  
Broad Spectrum ◽  
Molecular Targets ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Comparative Genomic ◽  
Multiple Resistance ◽  
Antibacterial Drugs ◽  
Trna Methyltransferase ◽  
Novel Targets ◽  
Quantitative Contribution

Single and multiple resistance to antibacterial drugs currently in use is spreading, since they act against only a very small number of molecular targets; finding novel targets for anti-infectives is therefore of great importance. All protein sequences from three pathogens (Staphylococcus aureus, Mycobacterium tuberculosisandEscherichia coliO157:H7 EDL993) were assessed via comparative genomics methods for their suitability as antibacterial targets according to a number of criteria, including the essentiality of the protein, its level of sequence conservation, and its distribution in pathogens, bacteria and eukaryotes (especially humans). Each protein was scored and ranked based on weighted variants of these criteria in order to prioritize proteins as potential novel broad-spectrum targets for antibacterial drugs. A number of proteins proved to score highly in all three species and were robust to variations in the scoring system used. Sensitivity analysis indicated the quantitative contribution of each metric to the overall score. After further analysis of these targets, tRNA methyltransferase (trmD) and translation initiation factor IF-1 (infA) emerged as potential and novel antimicrobial targets very worthy of further investigation. The scoring strategy used might be of value in other areas of post-genomic drug discovery.

scholarly journals Molecular Structure and Functional Elucidation of IF-3 Protein of Chloroflexus Aurantiacus Involved in Protein Biosynthesis: An In-Silico Approach

2021 ◽  
Author(s):  
Abu Saim Mohammad Saikat
Keyword(s):  
Translation Initiation ◽  
Protein Interactions ◽  
In Silico ◽  
Tertiary Structure ◽  
Protein Biosynthesis ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Chloroflexus Aurantiacus ◽  
Protein Protein Interactions ◽  
Functional Interpretation

<p><i>Chloroflexus aurantiacus</i> is a thermophilic bacterium that produces a multitude of proteins within its genome. Bioinformatics strategies can facilitate comprehending this organism through functional and structural interpretation assessments. This study aimed to allocate the structure and function through an in-silico approach required for bacterial protein biosynthesis. This in-silico viewpoint provides copious properties, including the physicochemical properties, subcellular location, three-dimensional structure, protein-protein interactions, and functional elucidation of the protein (WP_012256288.1). The STRING program is utilized for the explication of protein-protein interactions. The in-silico investigation documented the protein's hydrophilic nature with predominantly alpha (α) helices in its secondary structure. The tertiary-structure model of the protein has been shown to exhibit reasonably high consistency based on various quality assessment methods. The functional interpretation suggested that the protein can act as a translation initiation factor, a protein required for translation and protein biosynthesis. Protein-protein interactions also demonstrated high credence that the protein interconnected with 30S ribosomal subunit involved in protein synthesis. This study is bioinformatically examined that the protein (WP_012256288.1) is affiliated in protein biosynthesis as a translation initiation factor IF-3 of <i>C. aurantiacus</i>. </p> <p> </p>

scholarly journals Selection of Reference Genes for qRT-PCR Analysis in Medicinal Plant Glycyrrhiza under Abiotic Stresses and Hormonal Treatments

Plants ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 1441
Author(s):  
Yuping Li ◽  
Xiaoju Liang ◽  
Xuguo Zhou ◽  
Zhigeng Wu ◽  
Ling Yuan ◽  
...  
Keyword(s):  
Abiotic Stresses ◽  
Reference Genes ◽  
Citrate Synthase ◽  
Expression Profiles ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Pcr Analysis ◽  
Congeneric Species ◽  
Qrt Pcr ◽  
Hormonal Treatments

Best known as licorice, Glycyrrhiza Linn., a genus of herbaceous perennial legume, has been used as a traditional herbal medicine in Asia and a flavoring agent for tobacco and food industry in Europe and America. Abiotic stresses and hormonal treatments can significantly impact the development and metabolism of secondary metabolites in Glycyrrhiza. To better understand the biosynthesis of the trace-amount bioactive compounds, we first screened for the suitable reference genes for quantitative real-time reverse transcription PCR (qRT-PCR) analysis in Glycyrrhiza. The expression profiles of 14 candidate reference genes, including Actin1 (ACT), Clathrin complex AP1 (CAC), Cyclophilin (CYP), Heat-shock protein 40 (DNAJ), Dehydration responsive element binding gene (DREB), Translation elongation factor1 (EF1), Ras related protein (RAN), Translation initiation factor (TIF1), β-Tubulin (TUB), Ubiquitin-conjugating enzyme E2 (UBC2), ATP binding-box transpoter 2 (ABCC2), COP9 signal compex subunit 3 (COPS3), Citrate synthase (CS), and R3H domain protein 2 (R3HDM2) from two congeneric species, Glycyrrhiza uralensis F. and Glycyrrhiza inflata B., were examined under abiotic stresses (osmotic and salinity) and hormonal treatments (Abscisic acid (ABA) and methyl jasmonic acid (MeJA)) using a panel of software, including geNorm, NormFinder, BestKeeper, and Delta CT. The overall stability, however, was provided by RefFinder, a comprehensive ranking system integrating inputs from all four algorithms. In G. uralensis, the most stable reference genes under osmotic stress, salt stress, ABA treatment, and MeJA treatment were TIF1, DNAJ, CS, and ABCC2 for leaves and DNAJ, DREB, CAC, and CAC for roots, respectively. In comparison, the top ranked genes were TUB, CAC, UBC2, and RAN for leaves and TIF1, ABCC2, CAC, and UBC2 for roots, respectively, under stress and hormonal treatments in G. inflata. ACT and TIF1, on the other hand, were the least stable genes under the most experimental conditions in the two congeneric species. Finally, our survey of the reference genes in legume shows that EF, ACT, UBC2, and TUB were the top choices for the abiotic stresses while EF, UBC2, CAC, and ABCC2 were recommended for the hormonal treatments in Leguminosae. Our combined results provide reliable normalizers for accurate gene quantifications in Glycyrrhiza species, which will allow us to exploit its medicinal potential in general and antiviral activities in particular.

scholarly journals mTORC1 amplifies the ATF4-dependent de novo serine-glycine pathway to supply glycine during TGF-β1–induced collagen biosynthesis

2019 ◽  
Vol 12 (582) ◽  
pp. eaav3048 ◽  
Author(s):  
Brintha Selvarajah ◽  
Ilan Azuelos ◽  
Manuela Platé ◽  
Delphine Guillotin ◽  
Ellen J. Forty ◽  
...  
Keyword(s):  
Amino Acid ◽  
Tissue Repair ◽  
Glucose Transporter ◽  
Transforming Growth Factor ◽  
De Novo ◽  
Tissue Injury ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Myofibroblast Differentiation ◽  
Glucose Transporter 1

The differentiation of fibroblasts into a transient population of highly activated, extracellular matrix (ECM)–producing myofibroblasts at sites of tissue injury is critical for normal tissue repair. Excessive myofibroblast accumulation and persistence, often as a result of a failure to undergo apoptosis when tissue repair is complete, lead to pathological fibrosis and are also features of the stromal response in cancer. Myofibroblast differentiation is accompanied by changes in cellular metabolism, including increased glycolysis, to meet the biosynthetic demands of enhanced ECM production. Here, we showed that transforming growth factor–β1 (TGF-β1), the key pro-fibrotic cytokine implicated in multiple fibrotic conditions, increased the production of activating transcription factor 4 (ATF4), the transcriptional master regulator of amino acid metabolism, to supply glucose-derived glycine to meet the amino acid requirements associated with enhanced collagen production in response to myofibroblast differentiation. We further delineated the signaling pathways involved and showed that TGF-β1–induced ATF4 production depended on cooperation between canonical TGF-β1 signaling through Smad3 and activation of mechanistic target of rapamycin complex 1 (mTORC1) and its downstream target eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1). ATF4, in turn, promoted the transcription of genes encoding enzymes of the de novo serine-glycine biosynthetic pathway and glucose transporter 1 (GLUT1). Our findings suggest that targeting the TGF-β1–mTORC1–ATF4 axis may represent a novel therapeutic strategy for interfering with myofibroblast function in fibrosis and potentially in other conditions, including cancer.

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