5 results on '"Bozzoni I"'
Search Results
2. microRNAs Modulate Spatial Memory in the Hippocampus and in the Ventral Striatum in a Region-Specific Manner
- Author
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Capitano, F., primary, Camon, J., additional, Ferretti, V., additional, Licursi, V., additional, De Vito, F., additional, Rinaldi, A., additional, Vincenti, S., additional, Mannironi, C., additional, Fragapane, P., additional, Bozzoni, I., additional, Oliverio, A., additional, Negri, R., additional, Presutti, C., additional, and Mele, Andrea, additional
- Published
- 2015
- Full Text
- View/download PDF
3. A Regulatory Circuitry Between Gria2, miR-409, and miR-495 Is Affected by ALS FUS Mutation in ESC-Derived Motor Neurons.
- Author
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Capauto D, Colantoni A, Lu L, Santini T, Peruzzi G, Biscarini S, Morlando M, Shneider NA, Caffarelli E, Laneve P, and Bozzoni I
- Subjects
- Amyotrophic Lateral Sclerosis pathology, Animals, Cell Differentiation genetics, Down-Regulation genetics, Gene Expression Profiling, Gene Expression Regulation, Mice, MicroRNAs genetics, Models, Biological, Protein Subunits genetics, Protein Subunits metabolism, RNA, Messenger genetics, RNA, Messenger metabolism, Receptors, AMPA metabolism, Spinal Cord pathology, Amyotrophic Lateral Sclerosis genetics, MicroRNAs metabolism, Motor Neurons metabolism, Mouse Embryonic Stem Cells pathology, Mutation genetics, RNA-Binding Protein FUS genetics, Receptors, AMPA genetics
- Abstract
Mutations in fused in sarcoma (FUS) cause amyotrophic lateral sclerosis (ALS). FUS is a multifunctional protein involved in the biogenesis and activity of several types of RNAs, and its role in the pathogenesis of ALS may involve both direct effects of disease-associated mutations through gain- and loss-of-function mechanisms and indirect effects due to the cross talk between different classes of FUS-dependent RNAs. To explore how FUS mutations impinge on motor neuron-specific RNA-based circuitries, we performed transcriptome profiling of small and long RNAs of motor neurons (MNs) derived from mouse embryonic stem cells carrying a FUS-P517L knock-in mutation, which is equivalent to human FUS-P525L, associated with a severe and juvenile-onset form of ALS. Combining ontological, predictive and molecular analyses, we found an inverse correlation between several classes of deregulated miRNAs and their corresponding mRNA targets in both homozygous and heterozygous P517L MNs. We validated a circuitry in which the upregulation of miR-409-3p and miR-495-3p, belonging to a brain-specific miRNA subcluster implicated in several neurodevelopmental disorders, produced the downregulation of Gria2, a subunit of the glutamate α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor with a significant role in excitatory neurotransmission. Moreover, we found that FUS was involved in mediating such miRNA repression. Gria2 alteration has been proposed to be implicated in MN degeneration, through disturbance of Ca
2+ homeostasis, which triggers a cascade of damaging "excitotoxic" events. The molecular cross talk identified highlights a role for FUS in excitotoxicity and in miRNA-dependent regulation of Gria2. This circuitry also proved to be deregulated in heterozygosity, which matches the human condition perfectly.- Published
- 2018
- Full Text
- View/download PDF
4. miR-135a Regulates Synaptic Transmission and Anxiety-Like Behavior in Amygdala.
- Author
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Mannironi C, Biundo A, Rajendran S, De Vito F, Saba L, Caioli S, Zona C, Ciotti T, Caristi S, Perlas E, Del Vecchio G, Bozzoni I, Rinaldi A, Mele A, and Presutti C
- Subjects
- Adaptor Proteins, Vesicular Transport genetics, Adaptor Proteins, Vesicular Transport metabolism, Amygdala pathology, Animals, Cell Line, Tumor, Excitatory Postsynaptic Potentials, Gene Expression Regulation, Gene Knockdown Techniques, Hippocampus pathology, Humans, Mice, Inbred C57BL, MicroRNAs genetics, Nerve Tissue Proteins genetics, Nerve Tissue Proteins metabolism, Neurons metabolism, RNA, Messenger genetics, RNA, Messenger metabolism, Stress, Physiological genetics, Amygdala metabolism, Amygdala physiopathology, Anxiety genetics, Anxiety physiopathology, Behavior, Animal, MicroRNAs metabolism, Synaptic Transmission genetics
- Abstract
MicroRNAs are a class of non-coding RNAs with a growing relevance in the regulation of gene expression related to brain function and plasticity. They have the potential to orchestrate complex phenomena, such as the neuronal response to homeostatic challenges. We previously demonstrated the involvement of miR-135a in the regulation of early stress response. In the present study, we examine the role of miR-135a in stress-related behavior. We show that the knockdown (KD) of miR-135a in the mouse amygdala induces an increase in anxiety-like behavior. Consistently with behavioral studies, electrophysiological experiments in acute brain slices indicate an increase of amygdala spontaneous excitatory postsynaptic currents, as a result of miR-135a KD. Furthermore, we presented direct evidences, by in vitro assays and in vivo miRNA overexpression in the amygdala, that two key regulators of synaptic vesicle fusion, complexin-1 and complexin-2, are direct targets of miR-135a. In vitro analysis of miniature excitatory postsynaptic currents on miR-135a KD primary neurons indicates unpaired quantal excitatory neurotransmission. Finally, increased levels of complexin-1 and complexin-2 proteins were detected in the mouse amygdala after acute stress, accordingly to the previously observed stress-induced miR-135a downregulation. Overall, our results unravel a previously unknown miRNA-dependent mechanism in the amygdala for regulating anxiety-like behavior, providing evidences of a physiological role of miR-135a in the modulation of presynaptic mechanisms of glutamatergic neurotransmission.
- Published
- 2018
- Full Text
- View/download PDF
5. TDP-43 regulates the microprocessor complex activity during in vitro neuronal differentiation.
- Author
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Di Carlo V, Grossi E, Laneve P, Morlando M, Dini Modigliani S, Ballarino M, Bozzoni I, and Caffarelli E
- Subjects
- Basic Helix-Loop-Helix Transcription Factors metabolism, Cell Differentiation drug effects, Cell Line, Tumor, Gene Expression Profiling, Gene Expression Regulation, Neoplastic drug effects, Gene Knockdown Techniques, Humans, MicroRNAs genetics, Models, Biological, Nerve Tissue Proteins metabolism, Neuroblastoma genetics, Neuroblastoma pathology, Proteasome Inhibitors pharmacology, Protein Binding drug effects, Protein Binding genetics, Proteins metabolism, RNA, Messenger genetics, RNA, Messenger metabolism, RNA-Binding Proteins, Ribonuclease III genetics, Ribonuclease III metabolism, Cell Differentiation genetics, DNA-Binding Proteins metabolism, MicroRNAs metabolism, Neurons cytology
- Abstract
TDP-43 (TAR DNA-binding protein 43) is an RNA-binding protein implicated in RNA metabolism at several levels. Even if ubiquitously expressed, it is considered as a neuronal activity-responsive factor and a major signature for neurological pathologies, making the comprehension of its activity in the nervous system a very challenging issue. TDP-43 has also been described as an accessory component of the Drosha-DGCR8 (DiGeorge syndrome critical region gene 8) microprocessor complex, which is crucially involved in basal and tissue-specific RNA processing events. In the present study, we exploited in vitro neuronal differentiation systems to investigate the TDP-43 demand for the microprocessor function, focusing on both its canonical microRNA biosynthetic activity and its alternative role as a post-transcriptional regulator of gene expression. Our findings reveal a novel role for TDP-43 as an essential factor that controls the stability of Drosha protein during neuronal differentiation, thus globally affecting the production of microRNAs. We also demonstrate that TDP-43 is required for the Drosha-mediated regulation of Neurogenin 2, a master gene orchestrating neurogenesis, whereas post-transcriptional control of Dgcr8, another Drosha target, resulted to be TDP-43-independent. These results implicate a previously uncovered contribution of TDP-43 in regulating the abundance and the substrate specificity of the microprocessor complex and provide new insights into TDP-43 as a key player in neuronal differentiation.
- Published
- 2013
- Full Text
- View/download PDF
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