Similar Datasets
Project description:This study was aimed at elucidating the mechanisms underlying activity-dependent gene regulation during LTP of mouse hippocampal CA3-CA1 synapses. Deep sequencing of the 3’ end of transcripts allowed to identify changes in APA induced 1 hour and 3 hours after LTP induction. We detected APA changes that only affected the 3'UTR (3'UTR-APA events) and APA changes that also affected the coding sequence (CDS-APA events).
2018-02-22 | GSE84643 | GEO
Project description:This study was aimed at elucidating the mechanisms underlying activity-dependent gene regulation during long-term potentiation (LTP) of mouse hippocampal CA3-CA1 synapses. Transcriptome analysis allowed to identify changes in gene expression and alternative splicing induced 1 hour and 3 hours after LTP induction.
2018-02-22 | GSE84503 | GEO
Project description:Long-lasting forms of synaptic plasticity that underlie learning and memory require new transcription and translation for their persistence. The remarkable polarity and compartmentalization of neurons raises questions about the spatial and temporal regulation of gene expression within neurons. Alternative cleavage and polyadenylation (APA) generates mRNA isoforms with different 3' untranslated regions (3'UTRs) and/or coding sequences. Changes in the 3'UTR composition of mRNAs can alter gene expression by regulating transcript localization, stability and/or translation, while changes in the coding sequences lead to mRNAs encoding distinct proteins. Using specialized 3' end deep sequencing methods, we undertook a comprehensive analysis of APA following induction of long-term potentiation (LTP) of mouse hippocampal CA3-CA1 synapses. We identified extensive LTP-induced APA changes, including a general trend of 3'UTR shortening and activation of intronic APA isoforms. Comparison with transcriptome profiling indicated that most APA regulatory events were uncoupled from changes in transcript abundance. We further show that specific APA regulatory events can impact expression of two molecules with known functions during LTP, including 3'UTR APA of Notch1 and intronic APA of Creb1. Together, our results reveal that activity-dependent APA provides an important layer of gene regulation during learning and memory.
| S-EPMC5727029 | biostudies-literature
Project description:Activity-Dependent Regulation of Alternative Cleavage and Polyadenylation (APA) During Hippocampal Long-Term Potentiation (LTP)
| PRJNA330721 | ENA
Project description:Genes containing multiple polyadenylation (polyA) sites express mRNA isoforms with variable 3’ untranslated regions (3’UTRs). We found that short and long 3’UTR isoforms were relatively more abundant when genes were highly and lowly expressed, respectively, in human and mouse cells. Consistently, upregulated and downregulated genes were more likely to have shortened and lengthened 3’UTRs, respectively, when genes changed expression under different cell conditions or in response to extracellular stimuli. Using nuclear run-on assays, we found that RNA polymerase II (Pol II) was more likely to pause at the polyA site of highly expressed genes than that of lowly expressed ones. Moreover, in line with the difference in polyA site usage, highly expressed genes tend to have higher H3K4me3 and H3K36me3 levels but a lower density of nucleosome around promoter-proximal polyA sites relative to distal ones. Taken together, our results indicate that the efficiency of 3’ end processing is generally coupled to transcriptional activity, leading to modulation of polyA site choice by transcription and thus connecting transcriptional control with post-transcriptional regulation via pre-mRNA processing. Nascent RNA sequencing of C2C12 cell
2011-08-15 | E-GEOD-26512 | biostudies-arrayexpress
Project description:Genes containing multiple pre-mRNA cleavage and polyadenylation sites, or polyA sites, express mRNA isoforms with variable 3' untranslated regions (UTRs). By systematic analysis of human and mouse transcriptomes, we found that short 3'UTR isoforms are relatively more abundant when genes are highly expressed whereas long 3'UTR isoforms are relatively more abundant when genes are lowly expressed. Reporter assays indicated that polyA site choice can be modulated by transcriptional activity through the gene promoter. Using global and reporter-based nuclear run-on assays, we found that RNA polymerase II is more likely to pause at the polyA site of highly expressed genes than that of lowly expressed ones. Moreover, highly expressed genes tend to have a lower level of nucleosome but higher H3K4me3 and H3K36me3 levels at promoter-proximal polyA sites relative to distal ones. Taken together, our results indicate that polyA site usage is generally coupled to transcriptional activity, leading to regulation of alternative polyadenylation by transcription.
| S-EPMC3202805 | biostudies-other
Project description:To identify proteins involved in activity dependent synaptic remodeling that are not caused by changes in mRNA levels we performed RNA-seq and TMT-based quantitative MS.
2021-02-20 | GSE110908 | GEO
Project description:BACKGROUND: Erythropoietin (EPO) improves cognition of human subjects in the clinical setting by as yet unknown mechanisms. We developed a mouse model of robust cognitive improvement by EPO to obtain the first clues of how EPO influences cognition, and how it may act on hippocampal neurons to modulate plasticity. RESULTS: We show here that a 3-week treatment of young mice with EPO enhances long-term potentiation (LTP), a cellular correlate of learning processes in the CA1 region of the hippocampus. This treatment concomitantly alters short-term synaptic plasticity and synaptic transmission, shifting the balance of excitatory and inhibitory activity. These effects are accompanied by an improvement of hippocampus dependent memory, persisting for 3 weeks after termination of EPO injections, and are independent of changes in hematocrit. Networks of EPO-treated primary hippocampal neurons develop lower overall spiking activity but enhanced bursting in discrete neuronal assemblies. At the level of developing single neurons, EPO treatment reduces the typical increase in excitatory synaptic transmission without changing the number of synaptic boutons, consistent with prolonged functional silencing of synapses. CONCLUSION: We conclude that EPO improves hippocampus dependent memory by modulating plasticity, synaptic connectivity and activity of memory-related neuronal networks. These mechanisms of action of EPO have to be further exploited for treating neuropsychiatric diseases.
| S-EPMC2562991 | biostudies-literature
Project description:Alternative polyadenylation (APA) is a widespread gene regulatory mechanism that generates mRNAs with different 3'-ends, allowing them to interact with different sets of RNA regulators such as microRNAs and RNA-binding proteins. Recent studies have shown that during development, neural tissues produce mRNAs with particularly long 3'UTRs, suggesting that such extensions might be important for neural development and function. Despite this, the mechanisms underlying neural APA are not well understood. Here, we investigate this problem within the Drosophila nervous system, focusing on the roles played by general cleavage and polyadenylation factors (CPA factors). In particular, we examine the model that modulations in CPA factor concentration may affect APA during development. For this, we first analyse the expression of the Drosophila orthologues of all mammalian CPA factors and note that their expression decreases during embryogenesis. In contrast to this global developmental decrease in CPA factor expression, we see that cleavage factor I (CFI) expression is actually elevated in the late embryonic central nervous system, suggesting that CFI might play a special role in neural tissues. To test this, we use the UAS/Gal4 system to deplete CFI proteins from neural tissue and observe that in this condition, multiple genes switch their APA patterns, demonstrating a role of CFI in APA control during Drosophila neural development. Furthermore, analysis of genes with 3'UTR extensions of different length leads us to suggest a novel relation between 3'UTR length and sensitivity to CPA factor expression. Our work thus contributes to the understanding of the mechanisms of APA control within the developing central nervous system.
| S-EPMC5656104 | biostudies-literature
Project description:Alternative polyadenylation (APA) is a crucial step in post-transcriptional regulation. Previous bioinformatic studies have mainly focused on the recognition of polyadenylation sites (PASs) in a given genomic sequence, which is a binary classification problem. Recently, computational methods for predicting the usage level of alternative PASs in the same gene have been proposed. However, all of them cast the problem as a non-quantitative pairwise comparison task and do not take the competition among multiple PASs into account. To address this, here we propose a deep learning architecture, Deep Regulatory Code and Tools for Alternative Polyadenylation (DeeReCT-APA), to quantitatively predict the usage of all alternative PASs of a given gene. To accommodate different genes with potentially different numbers of PASs, DeeReCT-APA treats the problem as a regression task with a variable-length target. Based on a convolutional neural network-long short-term memory (CNN-LSTM) architecture, DeeReCT-APA extracts sequence features with CNN layers, uses bidirectional LSTM to explicitly model the interactions among competing PASs, and outputs percentage scores representing the usage levels of all PASs of a gene. In addition to the fact that only our method can quantitatively predict the usage of all the PASs within a gene, we show that our method consistently outperforms other existing methods on three different tasks for which they are trained: pairwise comparison task, highest usage prediction task, and ranking task. Finally, we demonstrate that our method can be used to predict the effect of genetic variations on APA patterns and sheds light on future mechanistic understanding in APA regulation. Our code and data are available at https://github.com/lzx325/DeeReCT-APA-repo.
| S-EPMC9801043 | biostudies-literature