scholarly journals MicroRNAs in Cancer: From Gene Expression Regulation to the Metastatic Niche Reprogramming

2021 ◽  
Author(s):  
Ekaterina V. Semina ◽  
Karina D. Rysenkova ◽  
Konstantin E. Troyanovskiy ◽  
Anna A. Shmakova ◽  
Kseniya A. Rubina
Keyword(s):  
Gene Expression ◽  
Gene Expression Regulation ◽  
Regulation Of Gene Expression ◽  
Genome Project ◽  
Mirna Biogenesis ◽  
Special Focus ◽  
Premetastatic Niche ◽  
Cell Compartments ◽  
Tumor Neoangiogenesis ◽  
The Human Genome Project

Abstract By 2003, the Human Genome project had been completed; however, it turned out that 97% of genome sequences did not encode proteins. The explanation came later when it was found the untranslated DNA contain sequences for short microRNAs (miRNAs) and long noncoding RNAs that did not produce any mRNAs or tRNAs, but instead were involved in the regulation of gene expression. Initially identified in the cytoplasm, miRNAs have been found in all cell compartments, where their functions are not limited to the degradation of target mRNAs. miRNAs that are secreted into the extracellular space as components of exosomes or as complexes with proteins, participate in morphogenesis, regeneration, oncogenesis, metastasis, and chemoresistance of tumor cells. miRNAs play a dual role in oncogenesis: on one hand, they act as oncogene suppressors; on the other hand, they function as oncogenes themselves and inactivate oncosuppressors, stimulate tumor neoangiogenesis, and mediate immunosuppressive processes in the tumors, The review presents current concepts of the miRNA biogenesis and their functions in the cytoplasm and nucleus with special focus on the noncanonical mechanisms of gene regulation by miRNAs and involvement of miRNAs in oncogenesis, as well as the authors’ opinion on the role of miRNAs in metastasis and formation of the premetastatic niche.

RNA Modifications in the Central Nervous System

2020 ◽  
Author(s):  
Dan Ohtan Wang
Keyword(s):  
Gene Expression ◽  
Cell Function ◽  
Gene Expression Regulation ◽  
Spinal Injury ◽  
Regulation Of Gene Expression ◽  
Modified Nucleosides ◽  
Rna Modifications ◽  
The Central Nervous System ◽  
Post Transcriptional Regulation ◽  
The Brain

Epitranscriptomics, a recently emerged field to investigate post-transcriptional regulation of gene expression through enzyme-mediated RNA modifications, is rapidly evolving and integrating with neuroscience. Using a rich repertoire of modified nucleosides and strategically positioning them to the functionally important and evolutionarily conserved regions of the RNA, epitranscriptomics dictates RNA-mediated cell function. The new field is quickly changing our view of the genetic geography in the brain during development and plasticity, impacting major functions from cortical neurogenesis, circadian rhythm, learning and memory, to reward, addiction, stress, stroke, and spinal injury, etc. Thus understanding the molecular components and operational rules of this pathway is becoming a key for us to decipher the genetic code for brain development, function, and disease. What RNA modifications are expressed in the brain? What RNAs carry them and rely on them for function? Are they dynamically regulated? How are they regulated and how do they contribute to gene expression regulation and brain function? This chapter summarizes recent advances that are beginning to answer these questions.

scholarly journals Roles of Transposable Elements in the Different Layers of Gene Expression Regulation

2019 ◽  
Vol 20 (22) ◽  
pp. 5755 ◽  
Author(s):  
Denise Drongitis ◽  
Francesco Aniello ◽  
Laura Fucci ◽  
Aldo Donizetti
Keyword(s):  
Gene Expression ◽  
Transposable Elements ◽  
Gene Expression Regulation ◽  
Regulation Of Gene Expression ◽  
Chromatin Modification ◽  
Essential Element ◽  
Protein Translation ◽  
Expression Regulation ◽  
Molecular Processes ◽  
Eukaryotic Genomes

The biology of transposable elements (TEs) is a fascinating and complex field of investigation. TEs represent a substantial fraction of many eukaryotic genomes and can influence many aspects of DNA function that range from the evolution of genetic information to duplication, stability, and gene expression. Their ability to move inside the genome has been largely recognized as a double-edged sword, as both useful and deleterious effects can result. A fundamental role has been played by the evolution of the molecular processes needed to properly control the expression of TEs. Today, we are far removed from the original reductive vision of TEs as “junk DNA”, and are more convinced that TEs represent an essential element in the regulation of gene expression. In this review, we summarize some of the more recent findings, mainly in the animal kingdom, concerning the active roles that TEs play at every level of gene expression regulation, including chromatin modification, splicing, and protein translation.

Untraditional methods for targeting the kidney in transgenic mice

2003 ◽  
Vol 285 (6) ◽  
pp. F1027-F1033 ◽  
Author(s):  
Robert A. Bianco ◽  
Henry L. Keen ◽  
Julie L. Lavoie ◽  
Curt D. Sigmund
Keyword(s):  
Gene Expression ◽  
Human Genome Project ◽  
Target Gene ◽  
Cell Types ◽  
Experimental Models ◽  
Genome Project ◽  
Renal Physiology ◽  
Physiological Relevance ◽  
The Human Genome Project

With the completion of the human genome project and the sequencing of many genomes of experimental models, there is a pressing need to determine the physiological relevance of newly identified genes. Gene-targeting approaches have become an important tool in our arsenal to dissect the significance of genes expressed in many tissues. A wealth of experimental models has been made to assess the role of gene expression in renal function and development. The development of new and informative models is presently limited by the anatomic complexity of the kidney and the lack of cell-specific promoters to target the numerous diverse cell types in that organ. Because of this, new approaches may have to be developed. In this review, we will discuss several untraditional methods to target gene expression to the kidney. These approaches should provide some additional tricks and tools to help in developing additional informative models for studying renal physiology.

Factor XIII-A is involved in the regulation of gene expression in alternatively activated human macrophages

2010 ◽  
Vol 104 (10) ◽  
pp. 709-717 ◽  
Author(s):  
Dániel Töröcsik ◽  
Lajos Széles ◽  
György Paragh ◽  
Zsuzsa Rákosy ◽  
Helga Bárdos ◽  
...  
Keyword(s):  
Gene Expression ◽  
Factor Xiii ◽  
Gene Expression Regulation ◽  
Regulation Of Gene Expression ◽  
Wound Response ◽  
Interleukin 4 ◽  
Alternative Activation ◽  
Wild Type ◽  
Functional Clustering ◽  
Alternatively Activated

SummaryFactor XIII subunit A (FXIII-A) is one of the most overrepresented genes that is expressed during the alternative activation of macrophages. Based on its substrate profile and its cellular localisation, FXIII-A is thought to function as an intracellular/intranuclear transglutaminase. Our aim was to find role for the intracellular FXIII-A by comparing the microarray profiles of alternatively activated monocyte-derived macrophages. Microarray analyses of FXIII-A-deficient patients and healthy controls were evaluated, followed by functional clustering of the differentially expressed genes. After a 48-hour differentiation in the presence of interleukin 4 (IL4), 1,017 probes out of the 24,398 expressed in macrophages from FXIII-A- deficient samples were IL4 sensitive, while only 596 probes were IL4 sensitive in wild-type samples. Of these genes, 307 were induced in both the deficient and the wild-type macrophages. Our results revealed that FXIII-A has important role(s) in mediating gene expression changes in macrophages during alternative activation. Functional clustering of the target genes carried out using Cytoscape/BiNGO and Ingenuity Pathways Analysis programs showed that, in the absence of FXIII-A, the most prominent differences are related to immune functions and to wound response. Our findings suggest that functional impairment of macrophages at the level of gene expression regulation plays a role in the wound healing defects of FXIII-A-deficient patients.

scholarly journals Using pan RNA-seq analysis to reveal the ubiquitous existence of 5’ end and 3’ end small RNAs

2018 ◽  
Author(s):  
Xiaofeng Xu ◽  
Haishuo Ji ◽  
Zhi Cheng ◽  
Xiufeng Jin ◽  
Xue Yao ◽  
...  
Keyword(s):  
Gene Expression ◽  
Steady State ◽  
Small Rnas ◽  
Gene Expression Regulation ◽  
Regulation Of Gene Expression ◽  
Cost Effective ◽  
Rna Degradation ◽  
Point Of View ◽  
Rna Seq ◽  
Dsrna Cleavage

AbstractIn this study, we used pan RNA-seq analysis to reveal the ubiquitous existence of 5’ end and 3’ end small RNAs. 5’ and 3’ sRNAs alone can be used to annotate mitochondrial with 1-bp resolution and nuclear non-coding genes and identify new steady-state RNAs, which are usually from functional genes. Using 5’, 3’ and intronic sRNAs, we revealed that the enzymatic dsRNA cleavage and RNAi could involve in the RNA degradation and gene expression regulation of U1 snRNA in human. The further study of 5’, 3’ and intronic sRNAs help rediscover double-stranded RNA (dsRNA) cleavage, RNA interference (RNAi) and the regulation of gene expression, which challenges the classical theories. In this study, we provided a simple and cost effective way for the annotation of mitochondrial and nuclear non-coding genes and the identification of new steady-state RNAs, particularly long non-coding RNAs (lncRNAs). We also provided a different point of view for cancer and virus, based on the new discoveries of dsRNA cleavage, RNAi and the regulation of gene expression.

scholarly journals Promoter Proximal Pausing Limits Tumorous Growth Induced by the Yki Transcription Factor in Drosophila

Genetics ◽  
2020 ◽  
Vol 216 (1) ◽  
pp. 67-77 ◽  
Author(s):  
Sanket Nagarkar ◽  
Ruchi Wasnik ◽  
Pravallika Govada ◽  
Stephen Cohen ◽  
L. S. Shashidhara
Keyword(s):  
Gene Expression ◽  
Rna Polymerase Ii ◽  
Gene Expression Regulation ◽  
Regulation Of Gene Expression ◽  
Elongation Factor ◽  
Imaginal Discs ◽  
Link Type ◽  
Genome Wide ◽  
Wing Imaginal Discs ◽  
Tumorous Growth

Promoter proximal pausing (PPP) of RNA polymerase II has emerged as a crucial rate-limiting step in the regulation of gene expression. Regulation of PPP is brought about by complexes 7SK snRNP, P-TEFb (Cdk9/cycT), and the negative elongation factor (NELF), which are highly conserved from Drosophila to humans. Here, we show that RNAi-mediated depletion of bin3 or Hexim of the 7SK snRNP complex or depletion of individual components of the NELF complex enhances Yki-driven growth, leading to neoplastic transformation of Drosophila wing imaginal discs. We also show that increased CDK9 expression cooperates with Yki in driving neoplastic growth. Interestingly, overexpression of CDK9 on its own or in the background of depletion of one of the components of 7SK snRNP or the NELF complex necessarily, and specifically, needed Yki overexpression to cause tumorous growth. Genome-wide gene expression analyses suggested that deregulation of protein homeostasis is associated with tumorous growth of wing imaginal discs. As both Fat/Hippo/Yki pathway and PPP are highly conserved, our observations may provide insights into mechanisms of oncogenic function of YAP—the ortholog of Yki in humans.

scholarly journals Transcriptional Enhancers in Drosophila

Genetics ◽  
2020 ◽  
Vol 216 (1) ◽  
pp. 1-26 ◽  
Author(s):  
Stephen Small ◽  
David N. Arnosti
Keyword(s):  
Gene Expression ◽  
Critical Role ◽  
Regulation Of Gene Expression ◽  
Regulatory Elements ◽  
Comprehensive Analysis ◽  
Special Focus ◽  
Transcriptional Enhancers ◽  
Quantitative Understanding ◽  
Developmental Role

Key discoveries in Drosophila have shaped our understanding of cellular “enhancers.” With a special focus on the fly, this chapter surveys properties of these adaptable cis-regulatory elements, whose actions are critical for the complex spatial/temporal transcriptional regulation of gene expression in metazoa. The powerful combination of genetics, molecular biology, and genomics available in Drosophila has provided an arena in which the developmental role of enhancers can be explored. Enhancers are characterized by diverse low- or high-throughput assays, which are challenging to interpret, as not all of these methods of identifying enhancers produce concordant results. As a model metazoan, the fly offers important advantages to comprehensive analysis of the central functions that enhancers play in gene expression, and their critical role in mediating the production of phenotypes from genotype and environmental inputs. A major challenge moving forward will be obtaining a quantitative understanding of how these cis-regulatory elements operate in development and disease.

scholarly journals The Bioinformatics of Integrative Medical Insights: Proposals for an International Psycho-Social and Cultural Bioinformatics Project

2006 ◽  
Vol 1 ◽  
pp. 117863370600100 ◽  
Author(s):  
Ernest Rossi ◽  
Kathryn Rossi ◽  
Garret Yount ◽  
Mauro Cozzolino ◽  
Salvador Iannotti
Keyword(s):  
Gene Expression ◽  
International Collaboration ◽  
Creative Process ◽  
Human Genome Project ◽  
Brain Plasticity ◽  
New Technology ◽  
Modern Medicine ◽  
Genome Project ◽  
The Past ◽  
The Human Genome Project

We propose the formation of an International Psycho-Social and Cultural Bioinformatics Project (IPCBP) to explore the research foundations of Integrative Medical Insights (IMI) on all levels from the molecular-genomic to the psychological, cultural, social, and spiritual. Just as The Human Genome Project identified the molecular foundations of modern medicine with the new technology of sequencing DNA during the past decade, the IPCBP would extend and integrate this neuroscience knowledge base with the technology of gene expression via DNA/proteomic microarray research and brain imaging in development, stress, healing, rehabilitation, and the psychotherapeutic facilitation of existentional wellness. We anticipate that the IPCBP will require a unique international collaboration of, academic institutions, researchers, and clinical practioners for the creation of a new neuroscience of mind-body communication, brain plasticity, memory, learning, and creative processing during optimal experiential states of art, beauty, and truth. We illustrate this emerging integration of bioinformatics with medicine with a videotape of the classical 4-stage creative process in a neuroscience approach to psychotherapy.

scholarly journals The Role of lncRNAs in Gene Expression Regulation through mRNA Stabilization

2021 ◽  
Vol 7 (1) ◽  
pp. 3
Author(s):  
Maialen Sebastian-delaCruz ◽  
Itziar Gonzalez-Moro ◽  
Ane Olazagoitia-Garmendia ◽  
Ainara Castellanos-Rubio ◽  
Izortze Santin
Keyword(s):  
Gene Expression ◽  
Mrna Stability ◽  
Molecular Mechanisms ◽  
Rna Binding ◽  
Gene Expression Regulation ◽  
Rna Binding Proteins ◽  
Regulation Of Gene Expression ◽  
Mrna Stabilization ◽  
Living Organisms ◽  
Almost All

mRNA stability influences gene expression and translation in almost all living organisms, and the levels of mRNA molecules in the cell are determined by a balance between production and decay. Maintaining an accurate balance is crucial for the correct function of a wide variety of biological processes and to maintain an appropriate cellular homeostasis. Long non-coding RNAs (lncRNAs) have been shown to participate in the regulation of gene expression through different molecular mechanisms, including mRNA stabilization. In this review we provide an overview on the molecular mechanisms by which lncRNAs modulate mRNA stability and decay. We focus on how lncRNAs interact with RNA binding proteins and microRNAs to avoid mRNA degradation, and also on how lncRNAs modulate epitranscriptomic marks that directly impact on mRNA stability.

scholarly journals A description of the relationship in healthy longevity and aging-related disease: from gene to protein

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Xiaolin Ni ◽  
Zhaoping Wang ◽  
Danni Gao ◽  
Huiping Yuan ◽  
Liang Sun ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prolonged Exposure ◽  
Gene Expression Regulation ◽  
Regulation Of Gene Expression ◽  
Human Longevity ◽  
Form Complex ◽  
Genetic Characteristics ◽  
Age Related ◽  
The Relationship

AbstractHuman longevity is a complex phenotype influenced by both genetic and environmental factors. It is also known to be associated with various types of age-related diseases, such as Alzheimer’s disease (AD) and cardiovascular disease (CVD). The central dogma of molecular biology demonstrates the conversion of DNA to RNA to the encoded protein. These proteins interact to form complex cell signaling pathways, which perform various biological functions. With prolonged exposure to the environment, the in vivo homeostasis adapts to the changes, and finally, humans adopt the phenotype of longevity or aging-related diseases. In this review, we focus on two different states: longevity and aging-related diseases, including CVD and AD, to discuss the relationship between genetic characteristics, including gene variation, the level of gene expression, regulation of gene expression, the level of protein expression, both genetic and environmental influences and homeostasis based on these phenotypes shown in organisms.

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