Identification, Characterization, and Regulatory Mechanisms of a Novel EGR1 Splicing Isoform

EGR1 is a transcription factor expressed in many cell types that regulates genes involved in different biological processes including growth, proliferation, and apoptosis. Dysregulation of EGR1 expression has been associated with many pathological conditions such as tumors and brain diseases. Known molecular mechanisms underlying the control of EGR1 function include regulation of transcription, mRNA and protein stability, and post-translational modifications. Here we describe the identification of a splicing isoform for the human EGR1 gene. The newly identified splicing transcript encodes a shorter protein compared to the canonical EGR1. This isoform lacks a region belonging to the N-terminal activation domain and although it is capable of entering the nucleus, it is unable to activate transcription fully relative to the canonical isoform.

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A Comprehensive Analysis of the Role of hnRNP A1 Function and Dysfunction in the Pathogenesis of Neurodegenerative Disease

Frontiers in Molecular Biosciences ◽

10.3389/fmolb.2021.659610 ◽

2021 ◽

Vol 8 ◽

Author(s):

Joseph P. Clarke ◽

Patricia A. Thibault ◽

Hannah E. Salapa ◽

Michael C. Levin

Keyword(s):

Neurodegenerative Disease ◽

Muscular Atrophy ◽

Protein Translation ◽

Cell Types ◽

Telomere Maintenance ◽

Regulation Of Transcription ◽

Hnrnp A1 ◽

Post Translational Modifications ◽

Microrna Processing ◽

Nuclear Ribonucleoprotein

Heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) is a member of the hnRNP family of conserved proteins that is involved in RNA transcription, pre-mRNA splicing, mRNA transport, protein translation, microRNA processing, telomere maintenance and the regulation of transcription factor activity. HnRNP A1 is ubiquitously, yet differentially, expressed in many cell types, and due to post-translational modifications, can vary in its molecular function. While a plethora of knowledge is known about the function and dysfunction of hnRNP A1 in diseases other than neurodegenerative disease (e.g., cancer), numerous studies in amyotrophic lateral sclerosis, frontotemporal lobar degeneration, multiple sclerosis, spinal muscular atrophy, Alzheimer’s disease, and Huntington’s disease have found that the dysregulation of hnRNP A1 may contribute to disease pathogenesis. How hnRNP A1 mechanistically contributes to these diseases, and whether mutations and/or altered post-translational modifications contribute to pathogenesis, however, is currently under investigation. The aim of this comprehensive review is to first describe the background of hnRNP A1, including its structure, biological functions in RNA metabolism and the post-translational modifications known to modify its function. With this knowledge, the review then describes the influence of hnRNP A1 in neurodegenerative disease, and how its dysfunction may contribute the pathogenesis.

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From Genes to Transcripts, a Tightly Regulated Journey in Plasmodium

Frontiers in Cellular and Infection Microbiology ◽

10.3389/fcimb.2020.618454 ◽

2020 ◽

Vol 10 ◽

Author(s):

Thomas Hollin ◽

Karine G. Le Roch

Keyword(s):

Life Cycle ◽

Malaria Parasite ◽

Molecular Mechanisms ◽

Cell Types ◽

Regulatory Mechanisms ◽

Tight Control ◽

Control Of Gene Expression ◽

Human Malaria Parasite ◽

Stage Conversion ◽

The Past

Over the past decade, we have witnessed significant progresses in understanding gene regulation in Apicomplexa including the human malaria parasite, Plasmodium falciparum. This parasite possesses the ability to convert in multiple stages in various hosts, cell types, and environments. Recent findings indicate that P. falciparum is talented at using efficient and complementary molecular mechanisms to ensure a tight control of gene expression at each stage of its life cycle. Here, we review the current understanding on the contribution of the epigenome, atypical transcription factors, and chromatin organization to regulate stage conversion in P. falciparum. The adjustment of these regulatory mechanisms occurring during the progression of the life cycle will be extensively discussed.

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Expression, Regulation, and Functions of the Galectin-16 Gene in Human Cells and Tissues

Biomolecules ◽

10.3390/biom11121909 ◽

2021 ◽

Vol 11 (12) ◽

pp. 1909

Author(s):

Jennifer D. Kaminker ◽

Alexander V. Timoshenko

Keyword(s):

Tissue Specificity ◽

Molecular Mechanisms ◽

Current Knowledge ◽

Human Cells ◽

Brain Diseases ◽

Biological Processes ◽

Prediction Tools ◽

Human Protein Atlas ◽

Trophoblastic Differentiation ◽

Post Transcriptional Regulation

Galectins comprise a family of soluble β-galactoside-binding proteins, which regulate a variety of key biological processes including cell growth, differentiation, survival, and death. This paper aims to address the current knowledge on the unique properties, regulation, and expression of the galectin-16 gene (LGALS16) in human cells and tissues. To date, there are limited studies on this galectin, with most focusing on its tissue specificity to the placenta. Here, we report the expression and 8-Br-cAMP-induced upregulation of LGALS16 in two placental cell lines (BeWo and JEG-3) in the context of trophoblastic differentiation. In addition, we provide the results of a bioinformatics search for LGALS16 using datasets available at GEO, Human Protein Atlas, and prediction tools for relevant transcription factors and miRNAs. Our findings indicate that LGALS16 is detected by microarrays in diverse human cells/tissues and alters expression in association with cancer, diabetes, and brain diseases. Molecular mechanisms of the transcriptional and post-transcriptional regulation of LGALS16 are also discussed based on the available bioinformatics resources.

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Unc-13 homolog D mediates an antiviral effect of the chromosome 19 microRNA cluster miR-517a

Journal of Cell Science ◽

10.1242/jcs.246769 ◽

2020 ◽

Vol 134 (5) ◽

pp. jcs246769

Author(s):

Kamil Krawczynski ◽

Yingshi Ouyang ◽

Jean-Francois Mouillet ◽

Tianjiao Chu ◽

Carolyn B. Coyne ◽

...

Keyword(s):

Antiviral Activity ◽

Viral Replication ◽

Molecular Mechanisms ◽

Cell Types ◽

Antiviral Effect ◽

Mirna Cluster ◽

Biological Processes ◽

Chromosome 19 ◽

Gene Target ◽

Vesicular Stomatitis

ABSTRACTThe function of microRNAs (miRNAs) can be cell autonomous or communicated to other cell types and has been implicated in diverse biological processes. We previously demonstrated that miR-517a-3p (miR-517a), a highly expressed member of the chromosome 19 miRNA cluster (C19MC) that is transcribed almost exclusively in human trophoblasts, attenuates viral replication via induction of autophagy in non-trophoblastic recipient cells. However, the molecular mechanisms underlying these effects remain unknown. Here, we identified unc-13 homolog D (UNC13D) as a direct, autophagy-related gene target of miR-517a, leading to repression of UNC13D. In line with the antiviral activity of miR-517a, silencing UNC13D suppressed replication of vesicular stomatitis virus (VSV), whereas overexpression of UNC13D increased VSV levels, suggesting a role for UNC13D silencing in the antiviral activity of miR-517a. We also found that miR-517a activated NF-κB signaling in HEK-293XL cells expressing TLR8, but the effect was not specific to C19MC miRNA. Taken together, our results define mechanistic pathways that link C19MC miRNA with inhibition of viral replication.

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The Anti-Neuroinflammatory Role of Anthocyanins and Their Metabolites for the Prevention and Treatment of Brain Disorders

International Journal of Molecular Sciences ◽

10.3390/ijms21228653 ◽

2020 ◽

Vol 21 (22) ◽

pp. 8653

Author(s):

Joana F. Henriques ◽

Diana Serra ◽

Teresa C. P. Dinis ◽

Leonor M. Almeida

Keyword(s):

Neurological Disorders ◽

Fruits And Vegetables ◽

Molecular Mechanisms ◽

Brain Inflammation ◽

Brain Diseases ◽

Naturally Occurring ◽

Pathological Conditions ◽

Promising Strategy ◽

Prevention And Treatment

Anthocyanins are naturally occurring polyphenols commonly found in fruits and vegetables. Numerous studies have described that anthocyanin-rich foods may play a crucial role in the prevention and treatment of different pathological conditions, which have encouraged their consumption around the world. Anthocyanins exhibit a significant neuroprotective role, mainly due to their well-recognized antioxidant and anti-inflammatory properties. Neuroinflammation is an intricate process relevant in both homeostatic and pathological circumstances. Since the progression of several neurological disorders relies on neuroinflammatory process, targeting brain inflammation has been considered a promising strategy in those conditions. Recent data have shown the anti-neuroinflammatory abilities of many anthocyanins and of their metabolites in the onset and development of several neurological disorders. In this review, it will be discussed the importance and the applicability of these polyphenolic compounds as neuroprotective agents and it will be also scrutinized the molecular mechanisms underlying the modulation of neuroinflammation by these natural compounds in the context of several brain diseases.

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Oligodendroglial heterogeneity in time and space (NG2 glia in the CNS)

e-Neuroforum ◽

10.1515/s13295-015-0014-y ◽

2015 ◽

Vol 21 (3) ◽

Author(s):

Leda Dimou ◽

Michael Wegner

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Cell Population ◽

Cell Types ◽

Heterogeneous Population ◽

Adult Brain ◽

Regulatory Mechanisms ◽

Pathological Conditions ◽

The Central Nervous System ◽

Similarities And Differences

AbstractNG2 glia represent a neural cell population that expresses the proteoglycan NG2 and is distinct from other cell types of the central nervous system. While they generate oligodendrocytes and a subset of astrocytes during development, their progeny in the adult brain solely consists of oligodendrocytes and further NG2 glia. In the last years, it has become clear that NG2 glia represent a heterogeneous population of cells with different properties and potential. In this review we will first discuss the similarities and differences between NG2 glia of the developing and adult CNS, before we will describe the regulatory mechanisms in these cells to finally concentrate on the heterogeneity of NG2 glia under physiological and pathological conditions.

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p38δMAPK: Emerging Roles of a Neglected Isoform

International Journal of Cell Biology ◽

10.1155/2014/272689 ◽

2014 ◽

Vol 2014 ◽

pp. 1-12 ◽

Cited By ~ 9

Author(s):

Carol O’Callaghan ◽

Liam J. Fanning ◽

Orla P. Barry

Keyword(s):

Protein Kinase ◽

P38 Mapk ◽

Molecular Mechanisms ◽

Mitogen Activated Protein Kinase ◽

Biological Processes ◽

Cellular Processes ◽

Mapk Activity ◽

Pathological Conditions ◽

Mapk Signalling ◽

Mitogen Activated Protein

p38δmitogen activated protein kinase (MAPK) is a unique stress responsive protein kinase. While the p38 MAPK family as a whole has been implicated in a wide variety of biological processes, a specific role for p38δMAPK in cellular signalling and its contribution to both physiological and pathological conditions are presently lacking. Recent emerging evidence, however, provides some insights into specific p38δMAPK signalling. Importantly, these studies have helped to highlight functional similarities as well as differences between p38δMAPK and the other members of the p38 MAPK family of kinases. In this review we discuss the current understanding of the molecular mechanisms underlying p38δMAPK activity. We outline a role for p38δMAPK in important cellular processes such as differentiation and apoptosis as well as pathological conditions such as neurodegenerative disorders, diabetes, and inflammatory disease. Interestingly, disparate roles for p38δMAPK in tumour development have also recently been reported. Thus, we consider evidence which characterises p38δMAPK as both a tumour promoter and a tumour suppressor. In summary, while our knowledge of p38δMAPK has progressed somewhat since its identification in 1997, our understanding of this particular isoform in many cellular processes still strikingly lags behind that of its counterparts.

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Hypoxia-inducible factors in the kidney

AJP Renal Physiology ◽

10.1152/ajprenal.00071.2006 ◽

2006 ◽

Vol 291 (2) ◽

pp. F271-F281 ◽

Cited By ~ 206

Author(s):

Volker H. Haase

Keyword(s):

Ubiquitin Ligase ◽

Cell Types ◽

Biological Processes ◽

Hypoxia Inducible Factors ◽

Α Subunit ◽

Von Hippel Lindau ◽

Helix Loop Helix ◽

Pathological Conditions ◽

Expression Of Genes ◽

Oxygen Sensitive

Tissue hypoxia not only occurs under pathological conditions but is also an important microenvironmental factor that is critical for normal embryonic development. Hypoxia-inducible factors HIF-1 and HIF-2 are oxygen-sensitive basic helix-loop-helix transcription factors, which regulate biological processes that facilitate both oxygen delivery and cellular adaptation to oxygen deprivation. HIFs consist of an oxygen-sensitive α-subunit, HIF-α, and a constitutively expressed β-subunit, HIF-β, and regulate the expression of genes that are involved in energy metabolism, angiogenesis, erythropoiesis and iron metabolism, cell proliferation, apoptosis, and other biological processes. Under conditions of normal Po2, HIF-α is hydroxylated and targeted for rapid proteasomal degradation by the von Hippel-Lindau (VHL) E3-ubiquitin ligase. When cells experience hypoxia, HIF-α is stabilized and either dimerizes with HIF-β in the nucleus to form transcriptionally active HIF, executing the canonical hypoxia response, or it physically interacts with unrelated proteins, thereby enabling convergence of HIF oxygen sensing with other signaling pathways. In the normal, fully developed kidney, HIF-1α is expressed in most cell types, whereas HIF-2α is mainly found in renal interstitial fibroblast-like cells and endothelial cells. This review summarizes some of the most recent advances in the HIF field and discusses their relevance to renal development, normal kidney function and disease.

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Store depletion and calcium influx

Physiological Reviews ◽

10.1152/physrev.1997.77.4.901 ◽

1997 ◽

Vol 77 (4) ◽

pp. 901-930 ◽

Cited By ~ 1068

Author(s):

A. B. Parekh ◽

R. Penner

Keyword(s):

Molecular Mechanisms ◽

Calcium Influx ◽

Regulatory Mechanisms ◽

Patch Clamp Technique ◽

Electrophysiological Properties ◽

Entry Pathway ◽

Store Depletion ◽

Proliferation And Apoptosis ◽

Ca2 Channels ◽

Intense Research

Calcium influx in nonexcitable cells regulates such diverse processes as exocytosis, contraction, enzyme control, gene regulation, cell proliferation, and apoptosis. The dominant Ca2+ entry pathway in these cells is the store-operated one, in which Ca2+ entry is governed by the Ca2+ content of the agonist-sensitive intracellular Ca2+ stores. Only recently has a Ca2+ current been described that is activated by store depletion. The properties of this new current, called Ca2+ release-activated Ca2+ current (ICRAC), have been investigated in detail using the patch-clamp technique. Despite intense research, the nature of the signal that couples Ca2+ store content to the Ca2+ channels in the plasma membrane has remained elusive. Although ICRAC appears to be the most effective and widespread influx pathway, other store-operated currents have also been observed. Although the Ca2+ release-activated Ca2+ channel has not yet been cloned, evidence continues to accumulate that the Drosophila trp gene might encode a store-operated Ca2+ channel. In this review, we describe the historical development of the field of Ca2+ signaling and the discovery of store-operated Ca2+ currents. We focus on the electrophysiological properties of the prototype store-operated current ICRAC, discuss the regulatory mechanisms that control it, and finally consider recent advances toward the identification of molecular mechanisms involved in this ubiquitous and important Ca2+ entry pathway.

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MicroRNAs: Promising New Antiangiogenic Targets in Cancer

BioMed Research International ◽

10.1155/2014/878450 ◽

2014 ◽

Vol 2014 ◽

pp. 1-14 ◽

Cited By ~ 28

Author(s):

Sandra Gallach ◽

Silvia Calabuig-Fariñas ◽

Eloisa Jantus-Lewintre ◽

Carlos Camps

Keyword(s):

Cell Types ◽

Biological Processes ◽

Tumour Angiogenesis ◽

Proliferation And Apoptosis ◽

Sequence Complementarity ◽

Specific Proteins ◽

Health And Disease ◽

Multiple Cell ◽

Non Coding Rnas

MicroRNAs are one class of small, endogenous, non-coding RNAs that are approximately 22 nucleotides in length; they are very numerous, have been phylogenetically conserved, and involved in biological processes such as development, differentiation, cell proliferation, and apoptosis. MicroRNAs contribute to modulating the expression levels of specific proteins based on sequence complementarity with their target mRNA molecules and so they play a key role in both health and disease. Angiogenesis is the process of new blood vessel formation from preexisting ones, which is particularly relevant to cancer and its progression. Over the last few years, microRNAs have emerged as critical regulators of signalling pathways in multiple cell types including endothelial and perivascular cells. This review summarises the role of miRNAs in tumour angiogenesis and their potential implications as therapeutic targets in cancer.

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