scholarly journals Measuring mRNA translation in neuronal processes and somata by tRNA-FRET

2019 ◽  
Author(s):  
Bella Koltun ◽  
Sivan Ironi ◽  
Noga Gershoni-Emek ◽  
Iliana Barrera ◽  
Mohammad Hleihil ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Mrna Translation ◽  
Chemical Induction ◽  
Translational Machinery ◽  
Disease States ◽  
Neural Processes ◽  
Neuronal Processes ◽  
Health And Disease ◽  
Slow Transport ◽  
Temporal Localization

AbstractIn neurons, the specific spatial and temporal localization of protein synthesis is of great importance for function and survival. In this work, we visualized tRNA and protein synthesis events in fixed and live mouse primary cortical culture using fluorescently-labeled tRNAs. We were able to characterize the distribution and movement of tRNAs in different neuronal sub-compartments and to study their association with the ribosome. We found that tRNA motion in neural processes is lower than in somata and corresponds to patterns of slow transport mechanisms, and that larger tRNA puncta co-localize with translational machinery components and are likely the functional fraction. Furthermore, chemical induction of LTP in culture revealed GluR-dependent biphasic up-regulation of mRNA translation with a similar effect in dendrites and somata. Importantly, measurement of protein synthesis in neurons with high resolutions offers new insights into neuronal function in health and disease states.

scholarly journals Measuring mRNA translation in neuronal processes and somata by tRNA-FRET

2020 ◽  
Vol 48 (6) ◽  
pp. e32-e32 ◽  
Author(s):  
Bella Koltun ◽  
Sivan Ironi ◽  
Noga Gershoni-Emek ◽  
Iliana Barrera ◽  
Mohammad Hleihil ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Mrna Translation ◽  
Long Term Potentiation ◽  
Chemical Induction ◽  
Translational Machinery ◽  
Disease States ◽  
Term Potentiation ◽  
Neuronal Processes ◽  
Slow Transport ◽  
Temporal Localization

Abstract In neurons, the specific spatial and temporal localization of protein synthesis is of great importance for function and survival. Here, we visualized tRNA and protein synthesis events in fixed and live mouse primary cortical culture using fluorescently-labeled tRNAs. We were able to characterize the distribution and transport of tRNAs in different neuronal sub-compartments and to study their association with the ribosome. We found that tRNA mobility in neural processes is lower than in somata and corresponds to patterns of slow transport mechanisms, and that larger tRNA puncta co-localize with translational machinery components and are likely the functional fraction. Furthermore, chemical induction of long-term potentiation (LTP) in culture revealed up-regulation of mRNA translation with a similar effect in dendrites and somata, which appeared to be GluR-dependent 6 h post-activation. Importantly, measurement of protein synthesis in neurons with high resolutions offers new insights into neuronal function in health and disease states.

Regulation of mRNA Translation in Axons

2020 ◽  
Author(s):  
Priyanka Patel ◽  
Pabitra K. Sahoo ◽  
Amar N. Kar ◽  
Jeffery L. Twiss
Keyword(s):  
Protein Synthesis ◽  
Translational Regulation ◽  
Neuronal Cell ◽  
Mrna Translation ◽  
Neuronal Cell Body ◽  
Translational Machinery ◽  
Protein Synthesis Machinery ◽  
Neuronal Systems ◽  
Axonal Protein ◽  
Axonal Protein Synthesis

Axons can extend long distances from the neuronal cell body, and mRNA translation in axons is used to locally generate new proteins in these distal reaches of the neuron’s cytoplasm. Work over the past two decades has shown that axonal mRNA translation occurs in many different organisms and different neuronal systems. The field has progressed substantially over this time, moving from documenting mRNA translation in axons to understanding how axonal mRNA translation is regulated and what the protein products do for the neuron. Translational regulation in axons extends beyond merely controlling activity of the protein synthesis machinery. Transport of mRNAs into axons, stability of the mRNAs within the axons, and sequestration of mRNAs away from the translational machinery each contribute to determining what proteins are generated in axons, as well as when and where those proteins are generated within the axon. It is now known that thousands of different mRNAs can localize into axons. Based on unique responses to different axonal translation regulating stimuli and events, there clearly is specificity for when different mRNA populations are translated. How that specificity is driven is just now beginning to be understood, and studies emerging over the last five years point to multiple mechanisms for imparting specificity for regulation of axonal protein synthesis responses.

Hypoxic Pulmonary Vasoconstriction and Chronic Lung Disease

2013 ◽  
Vol 12 (3) ◽  
pp. 135-144 ◽  
Author(s):  
Erik R. Swenson
Keyword(s):  
Pulmonary Hypertension ◽  
Lung Disease ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
World Health ◽  
Disease States ◽  
Pulmonary Vasoconstriction ◽  
Local Ventilation ◽  
Pulmonary Vascular Endothelium ◽  
Health And Disease ◽  
Health Organization

Hypoxic vasoconstriction in the lung is a unique and fundamental characteristic of the pulmonary circulation. It functions in health and disease states to better preserve ventilation-perfusion matching by diverting blood flow to better ventilated regions when local ventilation is compromised. As more areas of lung become hypoxic either with high altitude or global lung disease, then hypoxic pulmonary vasoconstriction (HPV) becomes less effective in ventilation-perfusion matching and can lead to pulmonary hypertension. HPV is intrinsic to the vascular smooth muscle and its mechanisms remain poorly understood. In addition, the pulmonary vascular endothelium, red cells, lung innervation, and numerous circulating vasoactive agents also affect the strength of HPV. This review will discuss the pathophysiology of HPV and address its role in pulmonary hypertension associated with World Health Organization Group 3 diseases. When sustained beyond many hours, HPV may initiate pulmonary vascular remodeling and lead to more fixed and less oxygen-responsive pulmonary hypertension if the hypoxic stimulus is maintained.

In Vitro Immunodetection of Prothymosin Alpha in Normal and Pathological Conditions

2020 ◽  
Vol 27 (29) ◽  
pp. 4840-4854 ◽  
Author(s):  
Chrysoula-Evangelia Karachaliou ◽  
Hubert Kalbacher ◽  
Wolfgang Voelter ◽  
Ourania E. Tsitsilonis ◽  
Evangelia Livaniou
Keyword(s):  
Mammalian Cells ◽  
Therapeutic Potential ◽  
Prothymosin Alpha ◽  
Disease States ◽  
Leading Role ◽  
Tissue Extracts ◽  
Biologic Response ◽  
Health And Disease ◽  
Almost All

Prothymosin alpha (ProTα) is a highly acidic polypeptide, ubiquitously expressed in almost all mammalian cells and tissues and consisting of 109 amino acids in humans. ProTα is known to act both, intracellularly, as an anti-apoptotic and proliferation mediator, and extracellularly, as a biologic response modifier mediating immune responses similar to molecules termed as “alarmins”. Antibodies and immunochemical techniques for ProTα have played a leading role in the investigation of the biological role of ProTα, several aspects of which still remain unknown and contributed to unraveling the diagnostic and therapeutic potential of the polypeptide. This review deals with the so far reported antibodies along with the related immunodetection methodology for ProTα (immunoassays as well as immunohistochemical, immunocytological, immunoblotting, and immunoprecipitation techniques) and its application to biological samples of interest (tissue extracts and sections, cells, cell lysates and cell culture supernatants, body fluids), in health and disease states. In this context, literature information is critically discussed, and some concluding remarks are presented.

Focusing on mRNA Granules and Stalled Polysomes Amidst Diverse Mechanisms Underlying mRNA Transport, mRNA Storage, and Local Translation

2020 ◽  
Author(s):  
Mina N. Anadolu ◽  
Wayne S. Sossin
Keyword(s):  
Protein Synthesis ◽  
Liquid Phase ◽  
Mrna Translation ◽  
Rna Transport ◽  
P Bodies ◽  
Rna Granules ◽  
Mrna Granules ◽  
Transport Particle ◽  
As Stress ◽  
The Individual

In neurons, mRNAs are transported to distal sites to allow for localized protein synthesis. There are many diverse mechanisms underlying this transport. For example, an individual mRNA can be transported in an RNA transport particle that is tailored to the individual mRNA and its associated binding proteins. In contrast, some mRNAs are transported in liquid-liquid phase separated structures called neuronal RNA granules that are made up of multiple stalled polysomes, allowing for rapid initiation-independent production of proteins required for synaptic plasticity. Moreover, neurons have additional types of liquid-liquid phase–separated structures containing mRNA, such as stress granules and P bodies. This chapter discusses the relationships between all of these structures, what proteins distinguish them, and the possible roles they play in the complex control of mRNA translation at distal sites that allow neurons to use protein synthesis to refine their local proteome in many different ways.

Neuronal mRNA Translation in Addiction

2018 ◽  
Author(s):  
Emma Puighermanal ◽  
Emmanuel Valjent
Keyword(s):  
Structural Changes ◽  
Drugs Of Abuse ◽  
Mrna Translation ◽  
Cell Types ◽  
Behavioral Changes ◽  
Translational Machinery ◽  
Addictive Drugs ◽  
Specific Mrnas ◽  
Cell Type Specific ◽  
Future Work

Addictive drugs trigger persistent synaptic and structural changes in the neuronal reward circuits that are thought to underlie the development of drug-adaptive behavior. While transcriptional and epigenetic modifications are known to contribute to these circuit changes, accumulating evidence indicates that altered mRNA translation is also a key molecular mechanism. This chapter reviews recent studies demonstrating how addictive drugs alter protein synthesis and/or the translational machinery and how this leads to neuronal circuit remodeling and behavioral changes. Future work will determine precisely which neuronal circuits and cell types participate in these changes. The chapter summarizes current methodologies for identifying cell type-specific mRNAs whose translation is affected by drugs of abuse and gives recent examples of the mechanistic insights into addiction they provide.

scholarly journals Upregulation of 5′-terminal oligopyrimidine mRNA translation upon loss of the ARF tumor suppressor

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Kyle A. Cottrell ◽  
Ryan C. Chiou ◽  
Jason D. Weber
Keyword(s):  
Protein Synthesis ◽  
Tumor Cells ◽  
Ribosomal Proteins ◽  
Human Cancer ◽  
Mrna Translation ◽  
Ribosome Profiling ◽  
Translational Efficiency ◽  
Gene Encoding ◽  
Terminal Oligopyrimidine ◽  
Ribosome Export

AbstractTumor cells require nominal increases in protein synthesis in order to maintain high proliferation rates. As such, tumor cells must acquire enhanced ribosome production. How the numerous mutations in tumor cells ultimately achieve this aberrant production is largely unknown. The gene encoding ARF is the most commonly deleted gene in human cancer. ARF plays a significant role in regulating ribosomal RNA synthesis and processing, ribosome export into the cytoplasm, and global protein synthesis. Utilizing ribosome profiling, we show that ARF is a major suppressor of 5′-terminal oligopyrimidine mRNA translation. Genes with increased translational efficiency following loss of ARF include many ribosomal proteins and translation factors. Knockout of p53 largely phenocopies ARF loss, with increased protein synthesis and expression of 5′-TOP encoded proteins. The 5′-TOP regulators eIF4G1 and LARP1 are upregulated in Arf- and p53-null cells.

scholarly journals Correction of eIF2-dependent defects in brain protein synthesis, synaptic plasticity, and memory in mouse models of Alzheimer’s disease

2021 ◽  
Vol 14 (668) ◽  
pp. eabc5429
Author(s):  
Mauricio M. Oliveira ◽  
Mychael V. Lourenco ◽  
Francesco Longo ◽  
Nicole P. Kasica ◽  
Wenzhong Yang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Protein Synthesis ◽  
Synaptic Plasticity ◽  
Translation Initiation ◽  
Mrna Translation ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Postmortem Brain Tissue ◽  
Phosphorylated Eif2α

Neuronal protein synthesis is essential for long-term memory consolidation, and its dysregulation is implicated in various neurodegenerative disorders, including Alzheimer’s disease (AD). Cellular stress triggers the activation of protein kinases that converge on the phosphorylation of eukaryotic translation initiation factor 2α (eIF2α), which attenuates mRNA translation. This translational inhibition is one aspect of the integrated stress response (ISR). We found that postmortem brain tissue from AD patients showed increased phosphorylation of eIF2α and reduced abundance of eIF2B, another key component of the translation initiation complex. Systemic administration of the small-molecule compound ISRIB (which blocks the ISR downstream of phosphorylated eIF2α) rescued protein synthesis in the hippocampus, measures of synaptic plasticity, and performance on memory-associated behavior tests in wild-type mice cotreated with salubrinal (which inhibits translation by inducing eIF2α phosphorylation) and in both β-amyloid-treated and transgenic AD model mice. Thus, attenuating the ISR downstream of phosphorylated eIF2α may restore hippocampal protein synthesis and delay cognitive decline in AD patients.

scholarly journals Regulation of mRNA Translation by Hormone Receptors in Breast and Prostate Cancer

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3254
Author(s):  
Jianling Xie ◽  
Eric P. Kusnadi ◽  
Luc Furic ◽  
Luke A. Selth
Keyword(s):  
Prostate Cancer ◽  
Protein Synthesis ◽  
Causes Of Death ◽  
Hormone Receptors ◽  
Mrna Translation ◽  
Estrogen Receptor Α ◽  
Growth And Survival ◽  
Cancer Types ◽  
Breast And Prostate Cancer ◽  
Hormone Signalling

Breast and prostate cancer are the second and third leading causes of death amongst all cancer types, respectively. Pathogenesis of these malignancies is characterised by dysregulation of sex hormone signalling pathways, mediated by the estrogen receptor-α (ER) in breast cancer and androgen receptor (AR) in prostate cancer. ER and AR are transcription factors whose aberrant function drives oncogenic transcriptional programs to promote cancer growth and progression. While ER/AR are known to stimulate cell growth and survival by modulating gene transcription, emerging findings indicate that their effects in neoplasia are also mediated by dysregulation of protein synthesis (i.e., mRNA translation). This suggests that ER/AR can coordinately perturb both transcriptional and translational programs, resulting in the establishment of proteomes that promote malignancy. In this review, we will discuss relatively understudied aspects of ER and AR activity in regulating protein synthesis as well as the potential of targeting mRNA translation in breast and prostate cancer.

scholarly journals A Crosstalk between Diet, Microbiome and microRNA in Epigenetic Regulation of Colorectal Cancer

Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2428
Author(s):  
Małgorzata Guz ◽  
Witold Jeleniewicz ◽  
Anna Malm ◽  
Izabela Korona-Glowniak
Keyword(s):  
Colorectal Cancer ◽  
Gastrointestinal Tract ◽  
Gut Microbiota ◽  
Intestinal Microbiota ◽  
Current Knowledge ◽  
Vital Role ◽  
Disease States ◽  
Health And Disease ◽  
Dietary Components ◽  
Non Coding Rnas

A still growing interest between human nutrition in relation to health and disease states can be observed. Dietary components shape the composition of microbiota colonizing our gastrointestinal tract which play a vital role in maintaining human health. There is a strong evidence that diet, gut microbiota and their metabolites significantly influence our epigenome, particularly through the modulation of microRNAs. These group of small non-coding RNAs maintain cellular homeostasis, however any changes leading to impaired expression of miRNAs contribute to the development of different pathologies, including neoplastic diseases. Imbalance of intestinal microbiota due to diet is primary associated with the development of colorectal cancer as well as other types of cancers. In the present work we summarize current knowledge with particular emphasis on diet-microbiota-miRNAs axis and its relation to the development of colorectal cancer.

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