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 Enhancing gonadotrope gene expression through regulatory lncRNAs

Endocrinology ◽  
2021 ◽  
Author(s):  
Tal Refael ◽  
Philippa Melamed
Keyword(s):  
Gene Expression ◽  
Regulation Of Gene Expression ◽  
Regulatory Elements ◽  
Transcriptional Enhancers ◽  
Open Questions ◽  
A Cell ◽  
Non Coding Rnas ◽  
Distal Regulatory Elements ◽  
Gonadotropic Hormones ◽  
Shed Light

Abstract The world of long non-coding RNAs (lncRNAs) has opened up massive new prospects in understanding the regulation of gene expression. Not only are there seemingly almost infinite numbers of lncRNAs in the mammalian cell, but they have highly diverse mechanisms of action. In the nucleus, some are chromatin-associated, transcribed from transcriptional enhancers (eRNAs) and/or direct changes in the epigenetic landscape with profound effects on gene expression. The pituitary gonadotrope is responsible for activation of reproduction through production and secretion of appropriate levels of the gonadotropic hormones. As such, it exemplifies a cell whose function is defined through changes in developmental and temporal patterns of gene expression, including those that are hormonally-induced. Roles for diverse distal regulatory elements and eRNAs in gonadotrope biology have only just begun to emerge. Here, we will present an overview of the different kinds of lncRNAs that alter gene expression, and what is known about their roles in regulating some of the key gonadotrope genes. We will also review various screens that have detected differentially expressed pituitary lncRNAs associated with changes in reproductive state, and those whose expression is found to play a role in gonadotrope-derived non-functioning pituitary adenomas. We hope to shed light on this exciting new field, emphasize the open questions, and encourage research to illuminate the roles of lncRNAs in various endocrine systems.

scholarly journals Long non-coding RNAs in brain tumors

NAR Cancer ◽  
2021 ◽  
Vol 3 (1) ◽  
Author(s):  
Keisuke Katsushima ◽  
George Jallo ◽  
Charles G Eberhart ◽  
Ranjan J Perera
Keyword(s):  
Gene Expression ◽  
Brain Tumors ◽  
Brain Cancer ◽  
Regulation Of Gene Expression ◽  
Therapeutic Targets ◽  
Diagnostic Biomarkers ◽  
Cancer Pathogenesis ◽  
Current State ◽  
Non Coding Rnas ◽  
Post Transcriptional Regulation

Abstract Long non-coding RNAs (lncRNAs) have been found to be central players in the epigenetic, transcriptional and post-transcriptional regulation of gene expression. There is an accumulation of evidence on newly discovered lncRNAs, their molecular interactions and their roles in the development and progression of human brain tumors. LncRNAs can have either tumor suppressive or oncogenic functions in different brain cancers, making them attractive therapeutic targets and biomarkers for personalized therapy and precision diagnostics. Here, we summarize the current state of knowledge of the lncRNAs that have been implicated in brain cancer pathogenesis, particularly in gliomas and medulloblastomas. We discuss their epigenetic regulation as well as the prospects of using lncRNAs as diagnostic biomarkers and therapeutic targets in patients with brain tumors.

The Role of miR-210 in the Biological System: A Current Overview

2019 ◽  
Vol 84 (6) ◽  
pp. 233-239
Author(s):  
Xu Hui ◽  
Hisham Al-Ward ◽  
Fahmi Shaher ◽  
Chun-Yang Liu ◽  
Ning Liu
Keyword(s):  
Gene Expression ◽  
Regulation Of Gene Expression ◽  
Low Oxygen ◽  
Cellular Functions ◽  
Regulate Gene Expression ◽  
System A ◽  
Non Coding Rnas ◽  
Post Transcriptional Regulation ◽  
A Current

<b><i>Background:</i></b> MicroRNAs (miRNAs) represent a group of non-coding RNAs measuring 19–23 nucleotides in length and are recognized as powerful molecules that regulate gene expression in eukaryotic cells. miRNAs stimulate the post-transcriptional regulation of gene expression via direct or indirect mechanisms. <b><i>Summary:</i></b> miR-210 is highly upregulated in cells under hypoxia, thereby revealing its significance to cell endurance. Induction of this mRNA expression is an important feature of the cellular low-oxygen response and the most consistent and vigorous target of HIF. <b><i>Key Message:</i></b> miR-210 is involved in many cellular functions under the effect of HIF-1α, including the cell cycle, DNA repair, immunity and inflammation, angiogenesis, metabolism, and macrophage regulation. It also plays an important regulatory role in T-cell differentiation and stimulation.

Identification of a Gain-of-Function SNP Causing a New Model of α-Thalassaemia.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 523-523
Author(s):  
Marco De Gobbi ◽  
Vip Viprakasit ◽  
Pieter J. de Jong ◽  
Yuko Yoshinaga ◽  
Jan-Fang Cheng ◽  
...  
Keyword(s):  
Gene Expression ◽  
Binding Site ◽  
Globin Gene ◽  
Regulation Of Gene Expression ◽  
Histone H3 ◽  
Regulatory Elements ◽  
Causative Mutation ◽  
Regulatory Sequences ◽  
Chromosome 16 ◽  
Upstream Regulatory Sequences

Abstract The human α globin cluster includes an embryonic gene ζ and 2 fetal/adult genes (α2 and α1) arranged along the chromosome in the order in which they are expressed in development (5′-ζ-pseudoζ- αD- α2-α1-𝛉-3′). Fully activated expression of these genes in erythroid cells depends on upstream regulatory elements of which HS-40, located 40kb upstream of the cluster, appears to exert the greatest effect. We have recently shown that during terminal differentiation, key transcription factors (GATA-2, GATA-1, NF-E2, SCL complex) sequentially bind the α promoters and their regulatory elements and a domain of histone acetylation develops which eventually encompasses the entire α globin cluster including the upstream regulatory sequences. α-thalassemia most frequently results from deletions or point mutations affecting the structural α globin genes, but may also result from rare sporadic deletions which remove the upstream regulatory sequences. In a single family α globin expression was silenced by a mutation which drives an anti-sense RNA through the α gene. Alpha thalassemia may also result from inherited and acquired mutations in a trans-acting factor called ATRX. Over the past few years we have continued to screen for new mechanisms which lead to α thalassemia and thereby elucidate new principles underlying the regulation of gene expression in hemopoiesis. Here we describe a new mechanism of α thalassemia occurring in Pacific Islanders in whom we could detect no mutations or rearrangements in the α globin gene locus. Despite this, extensive genetic analysis showed unequivocally that the causative mutation is linked to the terminal 169kb of chromosome 16 (Viprakasit et al accompanying abstract). Analysis of globin synthesis, steady state RNA levels and detection of RNA in situ demonstrated that the mutation downregulates α globin transcription. To identify the mutation, we constructed a new BAC library from an affected homozygote, isolated and re-sequenced the candidate region and focussed further analysis on 8 SNPS within the α globin cluster, one of which creates a new GATA-1 binding site (GACA>GATA). Using primary erythroblasts from normal individuals and patients with this form of thalassemia, together with interspecific hybrids containing either the normal or abnormal copy of chromosome 16, we have shown that this SNP creates a new binding site in vivo for GATA-1 and the SCL complex. Furthermore, the chromatin at this site becomes activated as judged by acetylation of histone H3 and H4 (H3ac2 and H4ac4) and methylation of histone H3 (H3K4me2). Based on these data we postulate that an active transcriptional complex binding this new GATA site created by the SNP-mutation, could distract the upstream regulatory regions, which normally interact with the α globin promoter, and silence α globin gene expression. This model thus represents a new example of α globin gene down-regulation and a new mechanism by which gene expression can be perturbed during hemopoiesis.

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.

Muscling in on microarrays

2008 ◽  
Vol 33 (1) ◽  
pp. 124-129 ◽  
Author(s):  
Carl Virtanen ◽  
Mark Takahashi
Keyword(s):  
Gene Expression ◽  
High Throughput ◽  
Dna Microarrays ◽  
Gene Expression Analysis ◽  
Exercise Physiology ◽  
Regulation Of Gene Expression ◽  
Enormous Amount ◽  
Potential Applications ◽  
New Generation ◽  
Affect Gene Expression

Adaptations that are the result of exercise require a multitude of changes at the level of gene expression. The mechanisms involved in regulating these changes are many, and can occur at various points in the pathways that affect gene expression. The completion of the human genome sequence, along with the genomes of related species, has provided an enormous amount of information to help dissect and understand these pathways. High-throughput methods, such as DNA microarrays, were the first on the scene to take advantage of this wealth of information. A new generation of microarrays has now taken the next step in revealing the mechanisms controlling gene expression. Analysis of the regulation of gene expression can now be profiled in a high-throughput fashion. However, the application of this technology has yet to be fully realized in the exercise physiology community. This review will highlight some of the latest advances in microarrays and briefly discuss some potential applications to the field of exercise physiology.

Misregulation of the Dependence Receptor DCC and its Upstream lincRNA, LOC100287225, in Colorectal Cancer

2015 ◽  
Vol 103 (1) ◽  
pp. 40-43 ◽  
Author(s):  
Mina Kazemzadeh ◽  
Reza Safaralizadeh ◽  
Mohammad Ali HosseinPour feizi ◽  
Mohammad Hossein Somi ◽  
Behrooz Shokoohi
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Regulation Of Gene Expression ◽  
Cellular Processes ◽  
Qrt Pcr ◽  
Cis Regulation ◽  
Tumor Tissues ◽  
Non Coding Rnas ◽  
Colorectal Cancer Patients ◽  
Dependence Receptor

Background Long non-coding RNAs (lncRNAs), a class of regulatory RNAs, play a major role in various cellular processes. Long intergenic non-coding RNAs (lincRNAs), a subclass of lncRNAs, are involved in the trans- and cis-regulation of gene expression. In the case of cis-regulation, by recruiting chromatin-modifying complexes, lincRNAs influence adjacent gene expression. Methods We used quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR) to evaluate the coexpression of LOC100287225, a lincRNA, and DCC, one of its adjacent genes that is often decreased in colorectal cancer, in pairs of tumor and adjacent tumor-free tissues of 30 colorectal cancer patients. Results The qRT-PCR results revealed the misregulation of these genes during tumorigenesis. Their relative expression levels were significantly lower in tumor tissues than adjacent tumor-free tissues. However, the analysis found no significant correlation between reduced expression of these genes. Conclusions Our study demonstrated the concurrent misregulation of DCC and LOC100287225 in colorectal cancer.

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 The Causes and Consequences of Spatial Organization of the Genome in Regulation of Gene Expression

2021 ◽  
Vol 12 ◽  
Author(s):  
Marios Agelopoulos ◽  
Spyros Foutadakis ◽  
Dimitris Thanos
Keyword(s):  
Gene Expression ◽  
Spatial Organization ◽  
Protein Complexes ◽  
Regulation Of Gene Expression ◽  
Regulatory Elements ◽  
Current View ◽  
Regulation Of Expression ◽  
Time Space ◽  
Transcriptional Regulatory ◽  
Immune Related Genes

Regulation of gene expression in time, space and quantity is orchestrated by the functional interplay of cis-acting elements and trans-acting factors. Our current view postulates that transcription factors recognize enhancer DNA and read the transcriptional regulatory code by cooperative DNA binding to specific DNA motifs, thus instructing the recruitment of transcriptional regulatory complexes forming a plethora of higher-ordered multi-protein-DNA and protein-protein complexes. Here, we reviewed the formation of multi-dimensional chromatin assemblies implicated in gene expression with emphasis on the regulatory role of enhancer hubs as coordinators of stochastic gene expression. Enhancer hubs contain many interacting regulatory elements and represent a remarkably dynamic and heterogeneous network of multivalent interactions. A functional consequence of such complex interaction networks could be that individual enhancers function synergistically to ensure coordination, tight control and robustness in regulation of expression of spatially connected genes. In this review, we discuss fundamental paradigms of such inter- and intra- chromosomal associations both in the context of immune-related genes and beyond.

scholarly journals Identifying causal models between genetically regulated methylation patterns and gene expression in healthy colon tissue

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Anna Díez-Villanueva ◽  
Mireia Jordà ◽  
Robert Carreras-Torres ◽  
Henar Alonso ◽  
David Cordero ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Quantitative Trait Loci ◽  
Genetic Variants ◽  
Quantitative Trait ◽  
Regulation Of Gene Expression ◽  
Regulatory Elements ◽  
Colon Tissue ◽  
Tissue Samples ◽  
Trait Loci

Abstract Background DNA methylation is involved in the regulation of gene expression and phenotypic variation, but the inter-relationship between genetic variation, DNA methylation and gene expression remains poorly understood. Here we combine the analysis of genetic variants related to methylation markers (methylation quantitative trait loci: mQTLs) and gene expression (expression quantitative trait loci: eQTLs) with methylation markers related to gene expression (expression quantitative trait methylation: eQTMs), to provide novel insights into the genetic/epigenetic architecture of colocalizing molecular markers. Results Normal mucosa from 100 patients with colon cancer and 50 healthy donors included in the Colonomics project have been analyzed. Linear models have been used to find mQTLs and eQTMs within 1 Mb of the target gene. From 32,446 eQTLs previously detected, we found a total of 6850 SNPs, 114 CpGs and 52 genes interrelated, generating 13,987 significant combinations of co-occurring associations (meQTLs) after Bonferromi correction. Non-redundant meQTLs were 54, enriched in genes involved in metabolism of glucose and xenobiotics and immune system. SNPs in meQTLs were enriched in regulatory elements (enhancers and promoters) compared to random SNPs within 1 Mb of genes. Three colorectal cancer GWAS SNPs were related to methylation changes, and four SNPs were related to chemerin levels. Bayesian networks have been used to identify putative causal relationships among associated SNPs, CpG and gene expression triads. We identified that most of these combinations showed the canonical pathway of methylation markers causes gene expression variation (60.1%) or non-causal relationship between methylation and gene expression (33.9%); however, in up to 6% of these combinations, gene expression was causing variation in methylation markers. Conclusions In this study we provided a characterization of the regulation between genetic variants and inter-dependent methylation markers and gene expression in a set of 150 healthy colon tissue samples. This is an important finding for the understanding of molecular susceptibility on colon-related complex diseases.

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