Research Progress in the Molecular Functions of Plant mTERF Proteins

Present-day chloroplast and mitochondrial genomes contain only a few dozen genes involved in ATP synthesis, photosynthesis, and gene expression. The proteins encoded by these genes are only a small fraction of the many hundreds of proteins that act in chloroplasts and mitochondria. Hence, the vast majority, including components of organellar gene expression (OGE) machineries, are encoded by nuclear genes, translated into the cytosol and imported to these organelles. Consequently, the expression of nuclear and organellar genomes has to be very precisely coordinated. Furthermore, OGE regulation is crucial to chloroplast and mitochondria biogenesis, and hence, to plant growth and development. Notwithstanding, the molecular mechanisms governing OGE are still poorly understood. Recent results have revealed the increasing importance of nuclear-encoded modular proteins capable of binding nucleic acids and regulating OGE. Mitochondrial transcription termination factor (mTERF) proteins are a good example of this category of OGE regulators. Plant mTERFs are located in chloroplasts and/or mitochondria, and have been characterized mainly from the isolation and analyses of Arabidopsis and maize mutants. These studies have revealed their fundamental roles in different plant development aspects and responses to abiotic stress. Fourteen mTERFs have been hitherto characterized in land plants, albeit to a different extent. These numbers are limited if we consider that 31 and 35 mTERFs have been, respectively, identified in maize and Arabidopsis. Notwithstanding, remarkable progress has been made in recent years to elucidate the molecular mechanisms by which mTERFs regulate OGE. Consequently, it has been experimentally demonstrated that plant mTERFs are required for the transcription termination of chloroplast genes (mTERF6 and mTERF8), transcriptional pausing and the stabilization of chloroplast transcripts (MDA1/mTERF5), intron splicing in chloroplasts (BSM/RUG2/mTERF4 and Zm-mTERF4) and mitochondria (mTERF15 and ZmSMK3) and very recently, also in the assembly of chloroplast ribosomes and translation (mTERF9). This review aims to provide a detailed update of current knowledge about the molecular functions of plant mTERF proteins. It principally focuses on new research that has made an outstanding contribution to unravel the molecular mechanisms by which plant mTERFs regulate the expression of chloroplast and mitochondrial genomes.

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The expanding world of metabolic enzymes moonlighting as RNA binding proteins

Biochemical Society Transactions ◽

10.1042/bst20200664 ◽

2021 ◽

Author(s):

Nicole J. Curtis ◽

Constance J. Jeffery

Keyword(s):

Gene Expression ◽

Regulatory Networks ◽

Binding Proteins ◽

Molecular Mechanisms ◽

Rna Binding ◽

Rna Binding Proteins ◽

Molecular Structures ◽

Intermediary Metabolism ◽

The Many ◽

And Function

RNA binding proteins play key roles in many aspects of RNA metabolism and function, including splicing, transport, translation, localization, stability and degradation. Within the past few years, proteomics studies have identified dozens of enzymes in intermediary metabolism that bind to RNA. The wide occurrence and conservation of RNA binding ability across distant branches of the evolutionary tree suggest that these moonlighting enzymes are involved in connections between intermediary metabolism and gene expression that comprise far more extensive regulatory networks than previously thought. There are many outstanding questions about the molecular structures and mechanisms involved, the effects of these interactions on enzyme and RNA functions, and the factors that regulate the interactions. The effects on RNA function are likely to be wider than regulation of translation, and some enzyme–RNA interactions have been found to regulate the enzyme's catalytic activity. Several enzyme–RNA interactions have been shown to be affected by cellular factors that change under different intracellular and environmental conditions, including concentrations of substrates and cofactors. Understanding the molecular mechanisms involved in the interactions between the enzymes and RNA, the factors involved in regulation, and the effects of the enzyme–RNA interactions on both the enzyme and RNA functions will lead to a better understanding of the role of the many newly identified enzyme–RNA interactions in connecting intermediary metabolism and gene expression.

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Epigenetics

Oxford Textbook of Cancer Biology ◽

10.1093/med/9780198779452.003.0005 ◽

2019 ◽

pp. 56-70

Author(s):

Edward Hookway ◽

Nicholas Athanasou ◽

Udo Oppermann

Keyword(s):

Gene Expression ◽

Histone Deacetylases ◽

Molecular Mechanisms ◽

Current Knowledge ◽

Tumour Suppressor Genes ◽

Epigenetic Mechanisms ◽

Therapeutic Approaches ◽

Control Of Gene Expression ◽

Non Coding Rnas ◽

Epigenetic Processes

Epigenetics is a term that refers to a collection of diverse mechanisms that are important in both the control of gene expression and the transmission of this information during cell division. Epigenetic processes are deranged in many cancers, leading to a combination of inappropriate silencing of tumour suppressor genes and overexpression of oncogenes. In this chapter, the molecular mechanisms that underpin the major epigenetic processes of DNA methylation, histone modification, and non-coding RNAs will be described in both their normal physiological roles and in the context of cancer. The challenge of understanding the complexity of the interactions between different epigenetic mechanisms and the limitations of our current knowledge will be highlighted. Therapeutic approaches towards targeting deranged epigenetic processes will also be described, such as the use of small molecule inhibitors of histone deacetylases.

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STIM1 Deficiency Leads to Specific Down-Regulation of ITPR3 in SH-SY5Y Cells

International Journal of Molecular Sciences ◽

10.3390/ijms21186598 ◽

2020 ◽

Vol 21 (18) ◽

pp. 6598

Author(s):

Carlos Pascual-Caro ◽

Yolanda Orantos-Aguilera ◽

Irene Sanchez-Lopez ◽

Jaime de Juan-Sanz ◽

Jan B. Parys ◽

...

Keyword(s):

Gene Expression ◽

Molecular Mechanisms ◽

Ectopic Expression ◽

Neuronal Cell ◽

Atp Synthesis ◽

Transport Systems ◽

Synthesis Rate ◽

Physical Interaction ◽

Excitable Cells ◽

Protein Levels

STIM1 is an endoplasmic reticulum (ER) protein that modulates the activity of a number of Ca2+ transport systems. By direct physical interaction with ORAI1, a plasma membrane Ca2+ channel, STIM1 activates the ICRAC current, whereas the binding with the voltage-operated Ca2+ channel CaV1.2 inhibits the current through this latter channel. In this way, STIM1 is a key regulator of Ca2+ signaling in excitable and non-excitable cells, and altered STIM1 levels have been reported to underlie several pathologies, including immunodeficiency, neurodegenerative diseases, and cancer. In both sporadic and familial Alzheimer’s disease, a decrease of STIM1 protein levels accounts for the alteration of Ca2+ handling that compromises neuronal cell viability. Using SH-SY5Y cells edited by CRISPR/Cas9 to knockout STIM1 gene expression, this work evaluated the molecular mechanisms underlying the cell death triggered by the deficiency of STIM1, demonstrating that STIM1 is a positive regulator of ITPR3 gene expression. ITPR3 (or IP3R3) is a Ca2+ channel enriched at ER-mitochondria contact sites where it provides Ca2+ for transport into the mitochondria. Thus, STIM1 deficiency leads to a strong reduction of ITPR3 transcript and ITPR3 protein levels, a consequent decrease of the mitochondria free Ca2+ concentration ([Ca2+]mit), reduction of mitochondrial oxygen consumption rate, and decrease in ATP synthesis rate. All these values were normalized by ectopic expression of ITPR3 in STIM1-KO cells, providing strong evidence for a new mode of regulation of [Ca2+]mit mediated by the STIM1-ITPR3 axis.

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MAP Kinase Pathways in the YeastSaccharomyces cerevisiae

Microbiology and Molecular Biology Reviews ◽

10.1128/mmbr.62.4.1264-1300.1998 ◽

1998 ◽

Vol 62 (4) ◽

pp. 1264-1300 ◽

Cited By ~ 660

Author(s):

Michael C. Gustin ◽

Jacobus Albertyn ◽

Matthew Alexander ◽

Kenneth Davenport

Keyword(s):

Gene Expression ◽

Signaling Pathways ◽

Molecular Mechanisms ◽

Current Knowledge ◽

Regulation Of Gene Expression ◽

Mapk Cascade ◽

Mitogen Activated Protein Kinase ◽

Future Research ◽

Mapk Pathways ◽

Mapk Cascades

SUMMARY A cascade of three protein kinases known as a mitogen-activated protein kinase (MAPK) cascade is commonly found as part of the signaling pathways in eukaryotic cells. Almost two decades of genetic and biochemical experimentation plus the recently completed DNA sequence of the Saccharomyces cerevisiae genome have revealed just five functionally distinct MAPK cascades in this yeast. Sexual conjugation, cell growth, and adaptation to stress, for example, all require MAPK-mediated cellular responses. A primary function of these cascades appears to be the regulation of gene expression in response to extracellular signals or as part of specific developmental processes. In addition, the MAPK cascades often appear to regulate the cell cycle and vice versa. Despite the success of the gene hunter era in revealing these pathways, there are still many significant gaps in our knowledge of the molecular mechanisms for activation of these cascades and how the cascades regulate cell function. For example, comparison of different yeast signaling pathways reveals a surprising variety of different types of upstream signaling proteins that function to activate a MAPK cascade, yet how the upstream proteins actually activate the cascade remains unclear. We also know that the yeast MAPK pathways regulate each other and interact with other signaling pathways to produce a coordinated pattern of gene expression, but the molecular mechanisms of this cross talk are poorly understood. This review is therefore an attempt to present the current knowledge of MAPK pathways in yeast and some directions for future research in this area.

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Ovarian Cancer: Prevention, Detection, and Treatment of the Disease and its Recurrence. Molecular Mechanisms and Personalized Medicine Meeting Report

International Journal of Gynecological Cancer ◽

10.1097/igc.0b013e31826bd1f2 ◽

2012 ◽

Vol 22 (Supp 2) ◽

pp. S45-S57 ◽

Cited By ~ 21

Author(s):

Francesmary Modugno ◽

Robert P. Edwards

Keyword(s):

Ovarian Cancer ◽

Molecular Mechanisms ◽

Current Knowledge ◽

Biological Activities ◽

Treatment Modalities ◽

Meeting Report ◽

Technological Advances ◽

Genetic Mechanisms ◽

New Research

ObjectiveTo review the current understanding of the underlying molecular, biologic, and genetic mechanisms involved in ovarian cancer development and how these mechanisms can be targets for prevention, detection, and treatment of the disease and its recurrence.MethodsIn May 2012, we convened a meeting of researchers, clinicians, and consumer advocates to review the state of current knowledge on molecular mechanisms and identify fruitful areas for further investigations.ResultsThe meeting consisted of 7 scientific sessions ranging from Epidemiology, Early Detection, and Biology to Therapeutics and Quality of Life. Sessions consisted of talks and panel discussions by international leaders in ovarian cancer research. A special career development session by the Congressionally Directed Medical Research Program Department of Defense Ovarian Cancer Academy as well as an oral abstract and poster session showcased promising new research by junior scientists.ConclusionsTechnological advances in the last decade have increased our knowledge of the molecular mechanisms involved in a host of biological activities related to ovarian cancer. Understanding the role these mechanisms play in cancer initiation and progression will help lead to the development of prevention and treatment modalities that can be personalized to each patient, thereby helping to overcome this highly fatal malignancy.

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Revealing the bovine embryo transcript profiles during early in vivo embryonic development

Reproduction ◽

10.1530/rep-08-0533 ◽

2009 ◽

Vol 138 (1) ◽

pp. 95-105 ◽

Cited By ~ 21

Author(s):

Maud Vallée ◽

Isabelle Dufort ◽

Stéphanie Desrosiers ◽

Aurélie Labbe ◽

Catherine Gravel ◽

...

Keyword(s):

Gene Expression ◽

Embryonic Development ◽

Molecular Mechanisms ◽

Developmental Stages ◽

Current Knowledge ◽

Mrna Level ◽

Early Embryonic Development ◽

Bovine Embryo ◽

Rna Content

Gene expression profiling is proving to be a powerful approach for the identification of molecular mechanisms underlying complex cellular functions such as the dynamic early embryonic development. The objective of this study was to perform a transcript abundance profiling analysis of bovine early embryonic development in vivo using a bovine developmental array. The molecular description of the first week of life at the mRNA level is particularly challenging when considering the important fluctuations in RNA content that occur between developmental stages. Accounting for the different intrinsic RNA content between developmental stages was achieved by restricting the reaction time during the global amplification steps and by using spiked controls and reference samples. Analysis based on intensity values revealed that most of the transcripts on the array were present at some point during in vivo bovine early embryonic development, while the varying number of genes detected in each developmental stage confirmed the dynamic profile of gene expression occurring during embryonic development. Pair-wise comparison of gene expression showed a marked difference between oocytes and blastocysts profiles, and principal component analysis revealed that the majority of the transcripts could be regrouped into three main clusters representing distinct RNA abundance profiles. Overall, these data provide a detailed temporal profile of the abundance of mRNAs revealing the richness of signaling processes in early mammalian development. Results presented here provide better knowledge of bovine in vivo embryonic development and contribute to the progression of our current knowledge regarding the first week of life in mammals.

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The Relevance of MicroRNAs in the Pathogenesis and Prognosis of HCV-Disease: The Emergent Role of miR-17-92 in Cryoglobulinemic Vasculitis

Viruses ◽

10.3390/v12121364 ◽

2020 ◽

Vol 12 (12) ◽

pp. 1364

Author(s):

Serena Lorini ◽

Laura Gragnani ◽

Anna Linda Zignego

Keyword(s):

Gene Expression ◽

Molecular Mechanisms ◽

Current Knowledge ◽

Public Health Problem ◽

Lymphoproliferative Disorders ◽

Major Public Health Problem ◽

Cryoglobulinemic Vasculitis ◽

Association Analyses ◽

Non Invasive

Hepatitis C virus (HCV) is a major public health problem. HCV is a hepatotropic and lymphotropic virus that leads to hepatocellular carcinoma (HCC) and lymphoproliferative disorders such as cryoglobulinemic vasculitis (CV) and non-Hodgkin’s lymphoma (NHL). The molecular mechanisms by which HCV induces these diseases are not fully understood. MicroRNAs (miRNAs) are small non-coding molecules that negatively regulate post-transcriptional gene expression by decreasing their target gene expression. We will attempt to summarize the current knowledge on the role of miRNAs in the HCV life cycle, HCV-related HCC, and lymphoproliferative disorders, focusing on both the functional effects of their deregulation as well as on their putative role as biomarkers, based on association analyses. We will also provide original new data regarding the miR 17-92 cluster in chronically infected HCV patients with and without lymphoproliferative disorders who underwent antiviral therapy. All of the cluster members were significantly upregulated in CV patients compared to patients without CV and significantly decreased in those who achieved vasculitis clinical remission after viral eradication. To conclude, miRNAs play an important role in HCV infection and related oncogenic processes, but their molecular pathways are not completely clear. In some cases, they may be potential therapeutic targets or non-invasive biomarkers of tumor progression.

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The many facets of bile acids in the physiology and pathophysiology of the human liver

Biological Chemistry ◽

10.1515/hsz-2021-0156 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Christoph G.W. Gertzen ◽

Holger Gohlke ◽

Dieter Häussinger ◽

Diran Herebian ◽

Verena Keitel ◽

...

Keyword(s):

Bile Acids ◽

Human Liver ◽

Molecular Mechanisms ◽

Current Knowledge ◽

Membrane Receptors ◽

Vital Functions ◽

Hereditary Disorders ◽

The Many ◽

Analytical Approaches ◽

G Protein Coupled

Abstract Bile acids perform vital functions in the human liver and are the essential component of bile. It is therefore not surprising that the biology of bile acids is extremely complex, regulated on different levels, and involves soluble and membrane receptors as well as transporters. Hereditary disorders of these proteins manifest in different pathophysiological processes that result in liver diseases of varying severity. In this review, we summarize our current knowledge of the physiology and pathophysiology of bile acids with an emphasis on recently established analytical approaches as well as the molecular mechanisms that underlie signaling and transport of bile acids. In this review, we will focus on ABC transporters of the canalicular membrane and their associated diseases. As the G protein-coupled receptor, TGR5, receives increasing attention, we have included aspects of this receptor and its interaction with bile acids.

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The Study of Cerebrospinal Fluid microRNAs in Spinal Cord Injury and Neurodegenerative Diseases: Methodological Problems and Possible Solutions

International Journal of Molecular Sciences ◽

10.3390/ijms23010114 ◽

2021 ◽

Vol 23 (1) ◽

pp. 114

Author(s):

Irina Baichurina ◽

Victor Valiullin ◽

Victoria James ◽

Albert Rizvanov ◽

Yana Mukhamedshina

Keyword(s):

Gene Expression ◽

Spinal Cord ◽

Spinal Cord Injury ◽

Cerebrospinal Fluid ◽

Neurodegenerative Diseases ◽

Neurological Disorders ◽

Molecular Mechanisms ◽

Current Knowledge ◽

Rna Isolation ◽

Cord Injury

Despite extensive research on neurological disorders, unanswered questions remain regarding the molecular mechanisms underpinning the course of these diseases, and the search continues for effective biomarkers for early diagnosis, prognosis, or therapeutic intervention. These questions are especially acute in the study of spinal cord injury (SCI) and neurodegenerative diseases. It is believed that the changes in gene expression associated with processes triggered by neurological disorders are the result of post-transcriptional gene regulation. microRNAs (miRNAs) are key regulators of post-transcriptional gene expression and, as such, are often looked to in the search for effective biomarkers. We propose that cerebrospinal fluid (CSF) is potentially a source of biomarkers since it is in direct contact with the central nervous system and therefore may contain biomarkers indicating neurodegeneration or damage to the brain and spinal cord. However, since the abundance of miRNAs in CSF is low, their isolation and detection is technically difficult. In this review, we evaluate the findings of recent studies of CSF miRNAs as biomarkers of spinal cord injury (SCI) and neurodegenerative diseases. We also summarize the current knowledge concerning the methods of studying miRNA in CSF, including RNA isolation and normalization of the data, highlighting the caveats of these approaches and possible solutions.

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Effects of Methanol on Carotenoids as Well as Biomass and Fatty Acid Biosynthesis in Schizochytrium limacinum B4D1

Applied and Environmental Microbiology ◽

10.1128/aem.01243-19 ◽

2019 ◽

Vol 85 (19) ◽

Cited By ~ 2

Author(s):

Huanmin Du ◽

Xiaoping Liao ◽

Zhengquan Gao ◽

Yang Li ◽

Yu Lei ◽

...

Keyword(s):

Gene Expression ◽

Fatty Acid ◽

Cell Growth ◽

Molecular Mechanisms ◽

Current Knowledge ◽

Expression Profiles ◽

Total Sterol ◽

Transcriptomic Analysis ◽

Schizochytrium Limacinum ◽

Promising Source

ABSTRACT Schizochytrium is a promising source for the production of docosahexaenoic acid and astaxanthin. The effects of different methanol concentrations on astaxanthin, biomass, and production of the lipids, squalene, and total sterol in Schizochytrium limacinum B4D1 were investigated. Astaxanthin began to accumulate when the methanol concentration reached 3.2% and peaked at 5.6% methanol, with a 2,000-fold increase over that in the control. However, under cultivation with 5.6% methanol, the biomass, lipids, squalene, and total sterol decreased to various degrees. Transcriptomic analysis was performed to explore the effects of different methanol concentrations (0%, 3.2%, and 5.6%) on the expression profile of B4D1. Three key signaling pathways were found to play important roles in regulating cell growth and metabolism under cultivation with methanol. Five central carbon metabolism-associated genes were significantly downregulated in response to 5.6% methanol and thus were expected to result in less ATP and NADPH being available for cell growth and synthesis. High methanol conditions significantly downregulated three genes involved in fatty acid and squalene/sterol precursor biosynthesis but significantly upregulated geranylgeranyl diphosphate synthase, lycopene β-cyclase, and β-carotene 3-hydroxylase, which are involved in astaxanthin synthesis, thus resulting in an increase in the levels of precursors and the final production of astaxanthin. Additionally, the transcriptional levels of three stress response genes were upregulated. This study investigates gene expression profiles in the astaxanthin producer Schizochytrium when grown under various methanol concentrations. These results broaden current knowledge regarding genetic expression and provide important information for promoting astaxanthin biosynthesis in Schizochytrium. IMPORTANCE Schizochytrium strains are usually studied as oil-producing strains, but they can also synthesize other secondary metabolites, such as astaxanthin. In this study, methanol was used as an inducer, and we explored its effects on the production of astaxanthin, a highly valuable substance in Schizochytrium. Methanol induced Schizochytrium to synthesize large amounts of astaxanthin. Transcriptomic analysis was used to investigate the regulation of signaling and metabolic pathways (mainly relative gene expression) in Schizochytrium grown in the presence of various concentrations of methanol. These results contribute to the understanding of the underlying molecular mechanisms and may aid in the future optimization of Schizochytrium for astaxanthin biosynthesis.

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