scholarly journals Citrullination – small change with a great consequence

2013 ◽  
Vol 9 ◽  
pp. 17-25 ◽  
Author(s):  
Mariusz Gogól
Keyword(s):  
Rheumatoid Arthritis ◽  
Gene Expression ◽  
Multiple Sclerosis ◽  
Positive Charge ◽  
Regulation Of Gene Expression ◽  
Slight Modification ◽  
Post Translational Modifications ◽  
Myelin Sheaths ◽  
Physiological Processes ◽  
Small Change

Citrullination is one of the possible post-translational modifications of proteins. It is based on a conversion of L-arginine residue (L-Arg) to L-citrulline residue (L-Cit). The reaction is catalyzed by peptidylarginine deiminases (PAD). The change of L-Arg imino moiety results in a loss of a positive charge. This slight modification can contribute to significant changes in physicochemical properties of proteins, which may also cause a change of their functions. Citrullination is the modification observed in physiological processes such as epidermal keratinization, regulation of gene expression and the reorganization of myelin sheaths. The changes in the efficacy of citrullination may contribute to the pathogenesis of many different diseases including: psoriasis, multiple sclerosis, rheumatoid arthritis and cancer.

scholarly journals Deimination, Intermediate Filaments and Associated Proteins

2020 ◽  
Vol 21 (22) ◽  
pp. 8746
Author(s):  
Julie Briot ◽  
Michel Simon ◽  
Marie-Claire Méchin
Keyword(s):  
Rheumatoid Arthritis ◽  
Multiple Sclerosis ◽  
Cell Differentiation ◽  
Intermediate Filaments ◽  
Cross Linking ◽  
Post Translational Modification ◽  
Innate And Adaptive Immunity ◽  
Calcium Dependent ◽  
Physiological Processes ◽  
Associated Proteins

Deimination (or citrullination) is a post-translational modification catalyzed by a calcium-dependent enzyme family of five peptidylarginine deiminases (PADs). Deimination is involved in physiological processes (cell differentiation, embryogenesis, innate and adaptive immunity, etc.) and in autoimmune diseases (rheumatoid arthritis, multiple sclerosis and lupus), cancers and neurodegenerative diseases. Intermediate filaments (IF) and associated proteins (IFAP) are major substrates of PADs. Here, we focus on the effects of deimination on the polymerization and solubility properties of IF proteins and on the proteolysis and cross-linking of IFAP, to finally expose some features of interest and some limitations of citrullinomes.

scholarly journals C5-Substituted 2-Selenouridines Ensure Efficient Base Pairing with Guanosine; Consequences for Reading the NNG-3′ Synonymous mRNA Codons

2020 ◽  
Vol 21 (8) ◽  
pp. 2882 ◽  
Author(s):  
Grazyna Leszczynska ◽  
Marek Cypryk ◽  
Bartlomiej Gostynski ◽  
Klaudia Sadowska ◽  
Paulina Herman ◽  
...  
Keyword(s):  
Gene Expression ◽  
Density Functional ◽  
Negative Charge ◽  
Positive Charge ◽  
Dominant Role ◽  
Regulation Of Gene Expression ◽  
Side Chain ◽  
Functional Theory ◽  
Physiological Conditions ◽  
Synonymous Codons

5-Substituted 2-selenouridines (R5Se2U) are post-transcriptional modifications present in the first anticodon position of transfer RNA. Their functional role in the regulation of gene expression is elusive. Here, we present efficient syntheses of 5-methylaminomethyl-2-selenouridine (1, mnm5Se2U), 5-carboxymethylaminomethyl-2-selenouridine (2, cmnm5Se2U), and Se2U (3) alongside the crystal structure of the latter nucleoside. By using pH-dependent potentiometric titration, pKa values for the N3H groups of 1–3 were assessed to be significantly lower compared to their 2-thio- and 2-oxo-congeners. At physiological conditions (pH 7.4), Se2-uridines 1 and 2 preferentially adopted the zwitterionic form (ZI, ca. 90%), with the positive charge located at the amino alkyl side chain and the negative charge at the Se2-N3-O4 edge. As shown by density functional theory (DFT) calculations, this ZI form efficiently bound to guanine, forming the so-called “new wobble base pair”, which was accepted by the ribosome architecture. These data suggest that the tRNA anticodons with wobble R5Se2Us may preferentially read the 5′-NNG-3′ synonymous codons, unlike their 2-thio- and 2-oxo-precursors, which preferentially read the 5′-NNA-3′ codons. Thus, the interplay between the levels of U-, S2U- and Se2U-tRNA may have a dominant role in the epitranscriptomic regulation of gene expression via reading of the synonymous 3′-A- and 3′-G-ending codons.

scholarly journals Circadian variations in gene expression in rat abdominal adipose tissue and relationship to physiology

2010 ◽  
Vol 42A (2) ◽  
pp. 141-152 ◽  
Author(s):  
Siddharth Sukumaran ◽  
Bai Xue ◽  
William J. Jusko ◽  
Debra C. DuBois ◽  
Richard R. Almon
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Circadian Rhythms ◽  
Regulation Of Gene Expression ◽  
Gene Array ◽  
Circadian Oscillation ◽  
Peripheral Tissues ◽  
Physiological Processes ◽  
Expression Of Genes ◽  
Rat Adipose Tissue

Circadian rhythms occur in all levels of organization from expression of genes to complex physiological processes. Although much is known about the mechanism of the central clock in the suprachiasmatic nucleus, the regulation of clocks present in peripheral tissues as well as the genes regulated by those clocks is still unclear. In this study, the circadian regulation of gene expression was examined in rat adipose tissue. A rich time series involving 54 animals euthanized at 18 time points within the 24-h cycle (12:12 h light-dark) was performed. mRNA expression was examined with Affymetrix gene array chips and quantitative real-time PCR, along with selected physiological measurements. Transcription factors involved in the regulation of central rhythms were examined, and 13 showed circadian oscillations. Mining of microarray data identified 190 probe sets that showed robust circadian oscillations. Circadian regulated probe sets were further parsed into seven distinct temporal clusters, with >70% of the genes showing maximum expression during the active/dark period. These genes were grouped into eight functional categories, which were examined within the context of their temporal expression. Circadian oscillations were also observed in plasma leptin, corticosterone, insulin, glucose, triglycerides, free fatty acids, and LDL cholesterol. Circadian oscillation in these physiological measurements along with the functional categorization of these genes suggests an important role for circadian rhythms in controlling various functions in white adipose tissue including adipogenesis, energy metabolism, and immune regulation.

scholarly journals Epigenetic Regulation of Myogenesis: Focus on the Histone Variants

2021 ◽  
Vol 22 (23) ◽  
pp. 12727
Author(s):  
Joana Esteves de Lima ◽  
Frédéric Relaix
Keyword(s):  
Gene Expression ◽  
Cell Fate ◽  
Epigenetic Regulation ◽  
Muscle Development ◽  
Regulation Of Gene Expression ◽  
Histone Variants ◽  
Myoblast Differentiation ◽  
Post Translational Modifications ◽  
Differentiation Status

Skeletal muscle development and regeneration rely on the successive activation of specific transcription factors that engage cellular fate, promote commitment, and drive differentiation. Emerging evidence demonstrates that epigenetic regulation of gene expression is crucial for the maintenance of the cell differentiation status upon division and, therefore, to preserve a specific cellular identity. This depends in part on the regulation of chromatin structure and its level of condensation. Chromatin architecture undergoes remodeling through changes in nucleosome composition, such as alterations in histone post-translational modifications or exchange in the type of histone variants. The mechanisms that link histone post-translational modifications and transcriptional regulation have been extensively evaluated in the context of cell fate and differentiation, whereas histone variants have attracted less attention in the field. In this review, we discuss the studies that have provided insights into the role of histone variants in the regulation of myogenic gene expression, myoblast differentiation, and maintenance of muscle cell identity.

scholarly journals A G(enomic)P(ositioning)S(ystem) for Plant RNAPII Transcription

2020 ◽  
Author(s):  
Sebastian Marquardt ◽  
Xueyuan Leng ◽  
Quentin Thomas ◽  
Simon Rasmussen
Keyword(s):  
Gene Expression ◽  
Histone Modifications ◽  
Regulation Of Gene Expression ◽  
Positioning System ◽  
Biological Functions ◽  
Post Translational Modifications ◽  
Histone Ptms ◽  
Definition Of ◽  
Generation Sequencing ◽  
Rnapii Transcription

Post-translational modifications (PTMs) of histone residues shape the landscape of gene expression by modulating the dynamic process of RNAPII transcription. The contribution of particular histone modifications to the definition of distinct RNAPII transcription stages remains poorly characterized in plants. Chromatin Immuno-precipitation combined with next-generation sequencing (ChIP-seq) resolves the genomic distribution of histone modifications. Here, we review histone PTM ChIP-seq data in Arabidopsis thaliana and find support for a Genomic Positioning System (GPS) that guides RNAPII transcription. We review the roles of histone PTM “readers”, “writers” and “erasers”, with a focus on the regulation of gene expression and biological functions in plants. The distinct functions of RNAPII transcription during the plant transcription cycle may in part rely on the characteristic histone PTMs profiles that distinguish transcription stages.

scholarly journals Many Routes from Glycolysis to Histone PTMs. Nature “Matters Arising” response to: Zhang et al. Metabolic regulation of gene expression by histone lactylation. (2019) Nature. 574(7779), 575-580.

2020 ◽  
Author(s):  
Chaitanya A. Kulkarni ◽  
Paul Brookes
Keyword(s):  
Gene Expression ◽  
Small Molecule ◽  
Metabolic Regulation ◽  
Regulation Of Gene Expression ◽  
Histone Mark ◽  
Acetyl Coa ◽  
Post Translational Modifications ◽  
Histone Ptms

Multiple histone post-translational modifications (PTMs) originate from small molecule metabolites (e.g. acetyl-lysine from acetyl-CoA) 1. As such, we read with interest the recent Nature paper from Zhang et al. 2 reporting discovery of lysine lactylation as a novel histone mark originating from the metabolite lactate. However, several concerns arise regarding the identity and source of this novel PTM.

scholarly journals Long Non-Coding RNAs in the Regulation of Gene Expression: Physiology and Disease

2019 ◽  
Vol 5 (1) ◽  
pp. 17 ◽  
Author(s):  
Juliane Fernandes ◽  
Stephanie Acuña ◽  
Juliana Aoki ◽  
Lucile Floeter-Winter ◽  
Sandra Muxel
Keyword(s):  
Gene Expression ◽  
Messenger Rna ◽  
Functional Characterization ◽  
Regulation Of Gene Expression ◽  
Regulatory Elements ◽  
Response Modulation ◽  
Physiological Processes ◽  
Interaction Domains ◽  
Non Coding Rnas ◽  
New Generation

The identification of RNAs that are not translated into proteins was an important breakthrough, defining the diversity of molecules involved in eukaryotic regulation of gene expression. These non-coding RNAs can be divided into two main classes according to their length: short non-coding RNAs, such as microRNAs (miRNAs), and long non-coding RNAs (lncRNAs). The lncRNAs in association with other molecules can coordinate several physiological processes and their dysfunction may impact in several pathologies, including cancer and infectious diseases. They can control the flux of genetic information, such as chromosome structure modulation, transcription, splicing, messenger RNA (mRNA) stability, mRNA availability, and post-translational modifications. Long non-coding RNAs present interaction domains for DNA, mRNAs, miRNAs, and proteins, depending on both sequence and secondary structure. The advent of new generation sequencing has provided evidences of putative lncRNAs existence; however, the analysis of transcriptomes for their functional characterization remains a challenge. Here, we review some important aspects of lncRNA biology, focusing on their role as regulatory elements in gene expression modulation during physiological and disease processes, with implications in host and pathogens physiology, and their role in immune response modulation.

scholarly journals Nutrient-Dependent Changes of Protein Palmitoylation: Impact on Nuclear Enzymes and Regulation of Gene Expression

2018 ◽  
Vol 19 (12) ◽  
pp. 3820 ◽  
Author(s):  
Matteo Spinelli ◽  
Salvatore Fusco ◽  
Claudio Grassi
Keyword(s):  
Gene Expression ◽  
Protein Trafficking ◽  
Regulation Of Gene Expression ◽  
Cysteine Modification ◽  
Post Translational Modifications ◽  
Protein Palmitoylation ◽  
Physiological Phenomenon ◽  
The Impact ◽  
Protein Lipidation

Diet is the main environmental stimulus chronically impinging on the organism throughout the entire life. Nutrients impact cells via a plethora of mechanisms including the regulation of both protein post-translational modifications and gene expression. Palmitoylation is the most-studied protein lipidation, which consists of the attachment of a molecule of palmitic acid to residues of proteins. S-palmitoylation is a reversible cysteine modification finely regulated by palmitoyl-transferases and acyl-thioesterases that is involved in the regulation of protein trafficking and activity. Recently, several studies have demonstrated that diet-dependent molecules such as insulin and fatty acids may affect protein palmitoylation. Here, we examine the role of protein palmitoylation on the regulation of gene expression focusing on the impact of this modification on the activity of chromatin remodeler enzymes, transcription factors, and nuclear proteins. We also discuss how this physiological phenomenon may represent a pivotal mechanism underlying the impact of diet and nutrient-dependent signals on human diseases.

scholarly journals Identification of hsa-miR-106a-5p as an impact agent on promotion of multiple sclerosis using multi-step data analysis

2020 ◽  
Author(s):  
Samira Rahimirad ◽  
Mohammad Navaderi ◽  
Shokoofeh Alaei ◽  
Mohammad Hossein Sanati
Keyword(s):  
Gene Expression ◽  
Multiple Sclerosis ◽  
Demyelinating Disease ◽  
Expression Patterns ◽  
Regulation Of Gene Expression ◽  
Blood Samples ◽  
Non Coding Rna ◽  
Healthy Control ◽  
Post Transcriptional Regulation ◽  
Signal Transductions

AbstractMultiple Sclerosis (MS) is a chronic, demyelinating disease in which the neuron myelin sheath is disrupted and leading to signal transductions disabilities. The evidence demonstrated that gene expression patterns and their related regulating factors are the most critical agents in Multiple Sclerosis demyelinating process. A miRNA is a small non-coding RNA which functions in post-transcriptional regulation of gene expression. Identification of specific miRNA dysregulation patterns in multiple sclerosis blood samples compared to healthy control can be used as a diagnostic and prognostic agent. Through the literature review and bioinformatics analysis, it was found that the hsa-miR-106a-5p can be considered as a significant MS pathogenic factor, which seems has an abnormal expression pattern in patients’ blood. Experimental validation using Real-Time PCR assay was carried to verifying the miR-106a-5p expression in Multiple Sclerosis and healthy control blood samples. The obtained results proved the miR-106a dysregulation in MS patients. The expression levels of miR-106a-5p were significantly down-regulated (Fold change=0.44) in patient blood samples compared to controls (p=0.059). Our study suggested that miR-106a-5p may have a biomarker potential to the diagnosis of MS patients based on its dysregulation patterns in Multiple Sclerosis blood.

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