scholarly journals Comprehensive catalog of dendritically localized mRNA isoforms from sub-cellular sequencing of single mouse neurons

2018 ◽  
Author(s):  
Sarah A. Middleton ◽  
James Eberwine ◽  
Junhyong Kim
Keyword(s):  
Hippocampal Neurons ◽  
Rna Localization ◽  
Synaptic Potentiation ◽  
Protein Structure Analysis ◽  
Mrna Isoforms ◽  
Neuronal Dendrites ◽  
Specific Localization ◽  
Dendritic Rna ◽  
Alternative Isoforms

AbstractRNA localization to neuronal dendrites is critical step for long-lasting synaptic potentiation, but there is little consensus regarding which RNAs are localized and the role of alternative isoforms in localization. Using independent RNA-sequencing from soma and dendrites of the same neuron, we deeply profiled the sub-cellular transcriptomes to assess the extent and variability of dendritic RNA localization in individual hippocampal neurons, including an assessment of differential localization of alternative 3’UTR isoforms. We identified 2,225 dendritic RNAs, including 298 cases of 3’UTR isoform-specific localization. We extensively analyzed the localized RNAs for potential localization motifs, finding that B1 and B2 SINE elements are up to 5.7 times more abundant in localized RNA 3’UTRs than non-localized, and also functionally characterized the localized RNAs using protein structure analysis. Finally, we integrate our list of localized RNAs with the literature to provide a comprehensive list of known dendritically localized RNAs as a resource.

scholarly journals The Role of Alternative Polyadenylation in the Regulation of Subcellular RNA Localization

2022 ◽  
Vol 12 ◽  
Author(s):  
Ankita Arora ◽  
Raeann Goering ◽  
Hei Yong G. Lo ◽  
Joelle Lo ◽  
Charlie Moffatt ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Molecular Mechanisms ◽  
Regulatory Mechanism ◽  
Alternative Polyadenylation ◽  
Mrna Localization ◽  
Rna Localization ◽  
Mrna Isoforms ◽  
Cellular Processes ◽  
Response To Stress

Alternative polyadenylation (APA) is a widespread and conserved regulatory mechanism that generates diverse 3′ ends on mRNA. APA patterns are often tissue specific and play an important role in cellular processes such as cell proliferation, differentiation, and response to stress. Many APA sites are found in 3′ UTRs, generating mRNA isoforms with different 3′ UTR contents. These alternate 3′ UTR isoforms can change how the transcript is regulated, affecting its stability and translation. Since the subcellular localization of a transcript is often regulated by 3′ UTR sequences, this implies that APA can also change transcript location. However, this connection between APA and RNA localization has only recently been explored. In this review, we discuss the role of APA in mRNA localization across distinct subcellular compartments. We also discuss current challenges and future advancements that will aid our understanding of how APA affects RNA localization and molecular mechanisms that drive these processes.

The role of exon II HTR2A transcript isoforms in the development of mental pathologies and antipsychotic therapy prognosis

2020 ◽  
pp. 24-26
Author(s):  
М.Н. Грунина ◽  
А.М. Заботина ◽  
А.С. Журавлев ◽  
Р.Ф. Насырова ◽  
А.Е. Тараскина
Keyword(s):  
Genetic Variant ◽  
Therapy Outcome ◽  
Gene Transcript ◽  
Antipsychotic Therapy ◽  
Transcript Isoforms ◽  
Alternative Isoforms ◽  
Htr2a Gene

Психические расстройства ассоциированы с нарушением паттерна изоформ транскриптов экзона II гена HTR2A за счет преобладания альтернативной изоформы Е2-. При этом высокий уровень экспрессии изоформы Е2- ассоциирован с благоприятным прогнозом антипсихотической терапии. The aim of the study was to analyze the role of exon II HTR2A gene transcript isoforms and rs6311 genetic variant in the development of mental pathologies and antipsychotic therapy prognosis. Alternative isoforms of exon II HTR2A are associated with the development of mental pathologies and is applicable to predict antipsychotic therapy outcome.

scholarly journals Downregulation of miR-383 reduces depression-like behavior through targeting Wnt family member 2 (Wnt2) in rats

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shanshan Liu ◽  
Qing Liu ◽  
Yanjie Ju ◽  
Lei Liu
Keyword(s):  
Inflammatory Response ◽  
Family Member ◽  
Chronic Stress ◽  
Hippocampal Neurons ◽  
Luciferase Reporter ◽  
Mild Stress ◽  
Neural Injury ◽  
Expression Levels ◽  
Qrt Pcr

AbstractThis study aimed to evaluate the role of miR-383 in the regulation of Wnt-2 signaling in the rat model of chronic stress. The male SD rats with depressive-like behaviors were stimulated with chronic unpredictable mild stress (CUMS) including ice-water swimming for 5 min, food deprivation for 24 h, water deprivation for 24 h, stimulating tail for 1 min, turning night into day, shaking for 15 min (once/s), and wrap restraint (5 min/time) every day for 21 days. The expression levels of miRNAs were detected by qRT-PCR, and the expression levels of Wnt2, depression-impacted proteins (GFAP, BDNF, CREB), brain neurotransmitters (5-HT, NE, DA) and apoptosis-related proteins (Bax and Bcl-2) were evaluated by qRT-PCR and western blot. Bioinformatic analysis and luciferase reporter assay were performed to determine the relationship between miR-383 and Wnt2. Ethological analysis was evaluated by sugar preference test, refuge island test and open field tests. Rescue experiments including knockdown of miR-383, overexpression and silencing of Wnt2 were performed to determine the role of miR-383. High expression levels of miR-383 were observed in the hippocampus of rats submitted to CUMS model. Downregulation of miR-383 significantly inhibited the apoptosis and inflammatory response of hippocampal neurons, and increased the expression levels of GFAP, BDNF and CREB which were impacted in depression, as well as neurotransmitters, then attenuated neural injury in rats induced by CUMS. Furthermore, Wnt family member 2 (Wnt2) was identified as a target of miR-383, and silencing of Wnt2 obviously attenuated the protective effect of miR-383 inhibitor on the apoptosis and inflammatory response in hippocampal neurons, as well as neural injury in CUMS-induced rats. Downregulation of miR-383 ameliorated the behavioral and neurochemical changes induced by chronic stress in rats by directly targeting Wnt2, indicating that the miR-383/Wnt2 axis might be a potential therapeutic target for MDD.

scholarly journals Role of Capsaicin-Sensitive C-Fiber Afferents in Neuropathic Pain-Induced Synaptic Potentiation in the Nociceptive Amygdala

2012 ◽  
Vol 8 ◽  
pp. 1744-8069-8-51 ◽  
Author(s):  
Ayano Nakao ◽  
Yukari Takahashi ◽  
Masashi Nagase ◽  
Ryo Ikeda ◽  
Fusao Kato
Keyword(s):  
Neuropathic Pain ◽  
Synaptic Potentiation ◽  
C Fiber

scholarly journals Deletion of the Actin-Associated Tropomyosin Tpm3 Leads to Reduced Cell Complexity in Cultured Hippocampal Neurons—New Insights into the Role of the C-Terminal Region of Tpm3.1

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 715
Author(s):  
Tamara Tomanić ◽  
Claire Martin ◽  
Holly Stefen ◽  
Esmeralda Parić ◽  
Peter Gunning ◽  
...  
Keyword(s):  
Amino Acid ◽  
Hippocampal Neurons ◽  
Molecular Mechanisms ◽  
Growth Cones ◽  
Amino Acid Residues ◽  
Terminal Amino Acid ◽  
C Terminus ◽  
Primary Mouse ◽  
Terminal Amino

Tropomyosins (Tpms) have been described as master regulators of actin, with Tpm3 products shown to be involved in early developmental processes, and the Tpm3 isoform Tpm3.1 controlling changes in the size of neuronal growth cones and neurite growth. Here, we used primary mouse hippocampal neurons of C57/Bl6 wild type and Bl6Tpm3flox transgenic mice to carry out morphometric analyses in response to the absence of Tpm3 products, as well as to investigate the effect of C-terminal truncation on the ability of Tpm3.1 to modulate neuronal morphogenesis. We found that the knock-out of Tpm3 leads to decreased neurite length and complexity, and that the deletion of two amino acid residues at the C-terminus of Tpm3.1 leads to more detrimental changes in neurite morphology than the deletion of six amino acid residues. We also found that Tpm3.1 that lacks the 6 C-terminal amino acid residues does not associate with stress fibres, does not segregate to the tips of neurites, and does not impact the amount of the filamentous actin pool at the axonal growth cones, as opposed to Tpm3.1, which lacks the two C-terminal amino acid residues. Our study provides further insight into the role of both Tpm3 products and the C-terminus of Tpm3.1, and it forms the basis for future studies that aim to identify the molecular mechanisms underlying Tpm3.1 targeting to different subcellular compartments.

The role of chloride transport in postsynaptic inhibition of hippocampal neurons

Science ◽  
1986 ◽  
Vol 232 (4756) ◽  
pp. 1413-1415 ◽  
Author(s):  
U Misgeld ◽  
R. Deisz ◽  
H. Dodt ◽  
H. Lux
Keyword(s):  
Hippocampal Neurons ◽  
Chloride Transport ◽  
Postsynaptic Inhibition

Ypsilon Schachtel, aDrosophilaY-box protein, acts antagonistically to Orb in theoskarmRNA localization and translation pathway

Development ◽  
2002 ◽  
Vol 129 (1) ◽  
pp. 197-209 ◽  
Author(s):  
Jennifer H. Mansfield ◽  
James E. Wilhelm ◽  
Tulle Hazelrigg
Keyword(s):  
Subcellular Localization ◽  
Essential Role ◽  
Genetic Interaction ◽  
Mrna Localization ◽  
Rna Localization ◽  
Essential Step ◽  
Positive Regulator ◽  
Body Patterning ◽  
Translational Regulators

Subcellular localization of mRNAs within the Drosophila oocyte is an essential step in body patterning. Yps, a Drosophila Y-box protein, is a component of an ovarian ribonucleoprotein complex that also contains Exu, a protein that plays an essential role in mRNA localization. Y-box proteins are known translational regulators, suggesting that this complex might regulate translation as well as mRNA localization. Here we examine the role of the yps gene in these events. We show that yps interacts genetically with orb, a positive regulator of oskar mRNA localization and translation. The nature of the genetic interaction indicates that yps acts antagonistically to orb. We demonstrate that Orb protein is physically associated with both the Yps and Exu proteins, and that this interaction is mediated by RNA. We propose a model wherein Yps and Orb bind competitively to oskar mRNA with opposite effects on translation and RNA localization.

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