scholarly journals Hecw controls oogenesis and neuronal homeostasis by promoting the liquid state of ribonucleoprotein particles

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Valentina Fajner ◽  
Fabio Giavazzi ◽  
Simona Sala ◽  
Amanda Oldani ◽  
Emanuele Martini ◽  
...  
Keyword(s):  
Molecular Level ◽  
Neuronal Loss ◽  
Premature Aging ◽  
Temporal Modulation ◽  
Embryonic Axes ◽  
Translational Repressor ◽  
Neuronal Homeostasis ◽  
Rnp Granules ◽  
Repressor Activity ◽  
Specific Mrna

AbstractSpecialised ribonucleoprotein (RNP) granules are a hallmark of polarized cells, like neurons and germ cells. Among their main functions is the spatial and temporal modulation of the activity of specific mRNA transcripts that allow specification of primary embryonic axes. While RNPs composition and role are well established, their regulation is poorly defined. Here, we demonstrate that Hecw, a newly identified Drosophila ubiquitin ligase, is a key modulator of RNPs in oogenesis and neurons. Hecw depletion leads to the formation of enlarged granules that transition from a liquid to a gel-like state. Loss of Hecw activity results in defective oogenesis, premature aging and climbing defects associated with neuronal loss. At the molecular level, reduced ubiquitination of the Fmrp impairs its translational repressor activity, resulting in altered Orb expression in nurse cells and Profilin in neurons.

scholarly journals The ubiquitin ligase Hecw controls oogenesis and neuronal homeostasis by promoting the liquid state of ribonucleoprotein particles

2020 ◽  
Author(s):  
Valentina Fajner ◽  
Fabio Giavazzi ◽  
Simona Sala ◽  
Amanda Oldani ◽  
Emanuele Martini ◽  
...  
Keyword(s):  
Ubiquitin Ligase ◽  
Neuronal Loss ◽  
Premature Aging ◽  
Main Function ◽  
Temporal Modulation ◽  
Embryonic Axes ◽  
Translational Repressor ◽  
Neuronal Homeostasis ◽  
Rnp Granules ◽  
Specific Mrna

Specialised ribonucleoprotein (RNP) granules are a hallmark of germ cells. Among their main function is the spatial and temporal modulation of the activity of specific mRNA transcripts that allow specification of primary embryonic axes. While RNPs composition and role are well established, their regulation is poorly defined. Here, we demonstrate that Hecw, a newly identified Drosophila ubiquitin ligase, is a key modulator of RNPs in oogenesis. Loss of Hecw activity results in the formation of enlarged granules that transition from a liquid to a gel-like state. At the molecular level, Hecw depletion leads to reduced ubiquitination and activity of the translational repressor Fmrp, resulting in premature Orb expression/recruitment in nurse cells. In addition to defective oogenesis, flies lacking Hecw show neurodegenerative traits with premature aging and climbing defects due to neuronal loss that are linked to RNPs condensation. Our findings reveal an unprecedented function of ubiquitin in modulating RNP fluidity and activity.

scholarly journals Strategies for the Identification of Novel Brain Specific Genes Affected in Alzheimer Disease

1989 ◽  
Vol 16 (S4) ◽  
pp. 483-489 ◽  
Author(s):  
D.G. Walker ◽  
B.E. Boyes ◽  
P.L. McGeer ◽  
E.G. McGeer
Keyword(s):  
Alzheimer Disease ◽  
Normal Cell ◽  
Temporal Cortex ◽  
Neuronal Loss ◽  
Brain Regions ◽  
Neuritic Plaques ◽  
Substantia Innominata ◽  
Expression Of Genes ◽  
Preliminary Description ◽  
Specific Mrna

ABSTRACT:The pathological changes that occur in Alzheimer disease (AD) brain lead to a large loss of various classes of neurons and the production of novel proteinaceous elements such as neuritic plaques and neurofibrillary tangles. For the neuronal loss to occur and these elements to arise, there must be a disturbance in the expression or regulation of genes that code for proteins required for normal cell maintenance, or perhaps even for the expression of genes unique to AD. We describe the construction of a cDNA library from the human substantia innominata and strategies for isolating genes that are expressed differentially between brain regions and which may be affected by AD. Some of the results obtained using these strategies and a preliminary description of a novel brain specific mRNA of 15.5kb, whose expression is increased in AD affected temporal cortex, are presented.

scholarly journals Astrocytic IGF-1 and IGF-1R Orchestrate Mitophagy in Traumatic Brain Injury

2020 ◽  
Author(s):  
Ren Dabin ◽  
Chen Wei ◽  
Shu Liang ◽  
Cao Ke ◽  
Wang Zhihan ◽  
...  
Keyword(s):  
Brain Injury ◽  
Cognitive Dysfunction ◽  
Molecular Level ◽  
Neuronal Loss ◽  
Proteomics Data ◽  
Non Coding Rnas ◽  
Brain Insults ◽  
Cognition Impairment ◽  
The Brain

Abstract Background Defective brain hormonal signaling and autophagy have been associated with neurodegeneration after brain insults, characterized by neuronal loss and cognitive dysfunction. However, less studies have link them in the context of brain injury. Insulin like growth factor-1 (IGF-1) is an important hormone that contributes to growth, cell proliferation and autophagy, also expressed in the brain. Methods We applied proteomics to investigate the role of astrocytic IGF-1 in TBI and related neuroprotective mechanisms. Results We found reduced plasma IGF-1 is correlated with cognition in TBI patients. Overexpression of astrocytic IGF-1 improves cognitive dysfunction in TBI mice and cocultured astrocytes prevent neuronal excitotoxicity with IGF-1 pathway dependent. At the molecular level, proteomics data show IGF-1 related NF-kB pathway transcriptionally regulates decapping mRNA2 (Dcp2) and miR-let-7, together with IGF-1R to orchestrate mitophagy in TBI. Finally, we demonstrate that TBI induces impaired mitophagy at the chronic stage and IGF-1 treatment could facilitate the mitophagy marker. Conclusion By showing that IGF-1 is an important mediator of the beneficial effect of neural-endocrine network in TBI models, our findings place IGF-1/IGF-1R as a potential target capable of non-coding RNAs and opposing mitophagy failure and cognition impairment in TBI.

scholarly journals Impacts of Macronutrients on Gene Expression: Recent Evidence to Understand Productive and Reproductive Performance of Livestock

2018 ◽  
Vol 6 (2) ◽  
pp. 203 ◽  
Author(s):  
Md. Mahmodul Hasan Sohel ◽  
Yusuf Konca ◽  
Mehmet Ulas Cinar
Keyword(s):  
Gene Expression ◽  
Reproductive Performance ◽  
Quantitative Measurement ◽  
Molecular Level ◽  
Specific Gene ◽  
Qpcr Array ◽  
Use Of Knowledge ◽  
The Impact ◽  
Generation Sequencing ◽  
Specific Mrna

In order to identify the effects of nutrients on gene expression and to assess the interactions between genes and nutrition by means of various cutting-edge technologies, the interdisciplinary branch ‘Nutrigenomics’ was created. Therefore, nutrigenomics corresponds to the use of knowledge and techniques of nutrition, genomics, transcriptomics, proteomics, epigenomics, and metabolomics to seek and explain the cross-talk between nutrition and genes in molecular level. Macronutrients are important dietary signals that control metabolic programming of cells and have important roles in maintaining cellular homeostasis by influencing specific gene expression. Recent advancements in molecular genetics studies, for instance, use of next-generation sequencing, microarray and qPCR array to investigate the expression of transcripts, genes, and miRNAs, has a crucial impact on understanding and quantitative measurement of the impact of dietary macronutrients on gene function. This review will shade a light on the interactions and mechanisms how the dietary source of macronutrients changes the expression of specific mRNA and miRNA. Furthermore, it will highlight the exciting recent findings in relation to animal performance characteristics which eventually help us to identify a dietary target to improve animal production.

scholarly journals Prospects on the nano-plastic particles internalization and induction of cellular response in human keratinocytes

2020 ◽  
Author(s):  
Ponnusamy Manogaran Gopinath ◽  
Krishna Sundar Twayana ◽  
Palaniyandi Ravanan ◽  
John Thomas ◽  
Amitava Mukherjee ◽  
...  
Keyword(s):  
Cellular Response ◽  
Molecular Level ◽  
Protein Corona ◽  
Human Keratinocytes ◽  
Premature Aging ◽  
Hacat Cells ◽  
Cytoprotective Effect ◽  
Cytotoxic Effects ◽  
Adsorbed Protein ◽  
Cell Growth And Proliferation

Abstract Background: Today cosmetic usage becomes customary in both sexes to improve their appearance and increase societal visibility. In this study, we have isolated nano-sized plastic particles ranging between 30 to 300 nm from the commercial face-scrubs and investigated its effects on keratinocytes. Results: Initially, nano-plastics adsorbed protein molecules and formed protein corona, thereby mimicked as protein aggregates, which then triggered the macropinocytosis activity. As a result, corrosion and degradation of plastic particles were observed. Concurrently, nano-plastics concentration-dependent cytotoxic, cytostatic, and cytoprotective activities were found in the keratinocytes. Additionally, a single dose of nano-plastics exposure for 48hrs resulted in the ROS mediated down-regulation of cell growth and proliferation inhibition followed by autophagy, finally, premature aging in HaCaT cells in 24 and 72 hrs of post-internalization, respectively. Conclusion: At the outset, this work provides insights into the nano-plastics concentration-dependent regulatory, cytoprotective, and cytotoxic effects in HaCaT cells. Further studies required to identify the detailed mechanisms of NPs toxicity on cells and the cytoprotective effect in cells at the molecular level.

Characterization of a maturation-specific mRNA in dry mung bean embryonic axes

Planta ◽  
1980 ◽  
Vol 149 (3) ◽  
pp. 227-233 ◽  
Author(s):  
Albert R. Carlier ◽  
A. Manickam ◽  
Willy J. Peumans
Keyword(s):  
Mung Bean ◽  
Embryonic Axes ◽  
Specific Mrna

scholarly journals Unraveling the Pathways to Neuronal Homeostasis and Disease: Mechanistic Insights into the Role of RNA-Binding Proteins and Associated Factors

2018 ◽  
Vol 19 (8) ◽  
pp. 2280 ◽  
Author(s):  
Stylianos Ravanidis ◽  
Fedon-Giasin Kattan ◽  
Epaminondas Doxakis
Keyword(s):  
Associated Factors ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Muscular Atrophy ◽  
Fragile X ◽  
Autism Spectrum ◽  
Cytoplasmic Inclusions ◽  
Neuronal Homeostasis ◽  
Rnp Granules

The timing, dosage and location of gene expression are fundamental determinants of brain architectural complexity. In neurons, this is, primarily, achieved by specific sets of trans-acting RNA-binding proteins (RBPs) and their associated factors that bind to specific cis elements throughout the RNA sequence to regulate splicing, polyadenylation, stability, transport and localized translation at both axons and dendrites. Not surprisingly, misregulation of RBP expression or disruption of its function due to mutations or sequestration into nuclear or cytoplasmic inclusions have been linked to the pathogenesis of several neuropsychiatric and neurodegenerative disorders such as fragile-X syndrome, autism spectrum disorders, spinal muscular atrophy, amyotrophic lateral sclerosis and frontotemporal dementia. This review discusses the roles of Pumilio, Staufen, IGF2BP, FMRP, Sam68, CPEB, NOVA, ELAVL, SMN, TDP43, FUS, TAF15, and TIA1/TIAR in RNA metabolism by analyzing their specific molecular and cellular function, the neurological symptoms associated with their perturbation, and their axodendritic transport/localization along with their target mRNAs as part of larger macromolecular complexes termed ribonucleoprotein (RNP) granules.

Preparatory Procedures for Electron Microscopic Analysis at the Molecular Level of Resolution

1978 ◽  
Vol 36 (3) ◽  
pp. 516-520
Author(s):  
F.J. Sjostrand
Keyword(s):  
Electron Microscope ◽  
Molecular Level ◽  
Microscopic Analysis ◽  
Resolving Power ◽  
Cellular Structures ◽  
Electron Microscopic ◽  
Systematic Analysis ◽  
Technical Developments ◽  
Thin Sectioning ◽  
Obvious Reason

In the 1940's and 1950's electron microscopy conferences were attended with everybody interested in learning about the latest technical developments for one very obvious reason. There was the electron microscope with its outstanding performance but nobody could make very much use of it because we were lacking proper techniques to prepare biological specimens. The development of the thin sectioning technique with its perfectioning in 1952 changed the situation and systematic analysis of the structure of cells could now be pursued. Since then electron microscopists have in general become satisfied with the level of resolution at which cellular structures can be analyzed when applying this technique. There has been little interest in trying to push the limit of resolution closer to that determined by the resolving power of the electron microscope.

RNA polymerase: Preparation and structural analysis of helical polymers

1984 ◽  
Vol 42 ◽  
pp. 152-153
Author(s):  
E. Loren Buhle ◽  
Pamela Rew ◽  
Ueli Aebi
Keyword(s):  
Structural Analysis ◽  
Rna Polymerase ◽  
Molecular Level ◽  
X Ray Diffraction ◽  
Helical Polymers ◽  
X Ray ◽  
E Coli ◽  
The Past ◽  
Ordered Arrays ◽  
Low Ionic Strength

While DNA-dependent RNA polymerase represents one of the key enzymes involved in transcription and ultimately in gene expression in procaryotic and eucaryotic cells, little progress has been made towards elucidation of its 3-D structure at the molecular level over the past few years. This is mainly because to date no 3-D crystals suitable for X-ray diffraction analysis have been obtained with this rather large (MW ~500 kd) multi-subunit (α2ββ'ζ). As an alternative, we have been trying to form ordered arrays of RNA polymerase from E. coli suitable for structural analysis in the electron microscope combined with image processing. Here we report about helical polymers induced from holoenzyme (α2ββ'ζ) at low ionic strength with 5-7 mM MnCl2 (see Fig. 1a). The presence of the ζ-subunit (MW 86 kd) is required to form these polymers, since the core enzyme (α2ββ') does fail to assemble into such structures under these conditions.

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