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Opto-CLIP reveals dynamic FMRP regulation of mRNAs upon CA1 neuronal activation [RiboTag]

ABSTRACT: Opto-CLIP reveals dynamic FMRP regulation of mRNAs upon CA1 neuronal activation [RiboTag]

PROVIDER: PRJNA1209014 | ENA |

REPOSITORIES: ENA

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Opto-CLIP reveals dynamic FMRP regulation of mRNAs upon CA1 neuronal activation [RiboTag]

Project description:Neuronal diversity and function are intricately linked to the dynamic regulation of RNA metabolism, including splicing, localization, and translation. Electrophysiologic studies of synaptic plasticity, models for learning and memory, are disrupted in Fragile X Syndrome (FXS). FXS is characterized by the loss of FMRP, an RNA-binding protein (RBP) known to bind and suppress translation of specific neuronal RNAs. Since molecular studies have demonstrated that synaptic plasticity in CA1 excitatory hippocampal neurons is protein-synthesis dependent, together these observations have suggested a potential role for FMRP in synaptic plasticity in FXS. To explore this model, we developed a new experimental platform, Opto-CLIP, to integrate optogenetics with cell-type specific FMRP CLIP and RiboTag in CA1 hippocampal neurons, allowing investigation of FMRP- regulated dynamics after neuronal activation. We tracked changes in FMRP binding and ribosome- associated RNA profiles 30 minutes after neuronal activation. Our findings reveal a significant reduction in FMRP-RNA binding to transcripts encoding nuclear proteins, suggesting FMRP translational inhibition may be de-repressed to allow rapid translational responses required for neuronal homeostasis. In contrast, FMRP binding to transcripts encoding synaptic targets were generally stable after activation, but all categories of targets demonstrated variability in FMRP translational control. Opto-CLIP revealed differential regulation of subsets of transcripts within CA1 neurons rapidly after depolarization, and offers promise as a generally useful platform to uncover mechanisms of RBP-mediated RNA regulation in the context of synaptic plasticity.

2025-01-15 | GSE286381 | GEO

Opto-CLIP reveals dynamic FMRP regulation of mRNAs upon CA1 neuronal activation [CLIP]

2025-01-15 | GSE286379 | GEO

FMRP regulates mRNAs encoding distinct functions in the cell body and dendrites of CA1 pyramidal neurons [FMRP-CLIP]

Project description:We report cell-type and compartment-specific TRAP-seq, RNAseq, FMRP-CLIP, and PAPERCLIP from CA1 hippocampal neurons. We use TRAP-seq and PAPERCLIP data to precisely define the dendritic transcriptome, including mRNAs that harbor APA and AS events that are differentially localized. Further, we use FMRP-CLIP in order to define mRNAs that undergo compartment-specific regulation by FMRP.

2022-05-11 | GSE180412 | GEO

FMRP cTag CLIP from mouse CA1 pyramidal neurons

Project description:Loss of the neuronal RNA binding protein FMRP causes Fragile X Syndrome (FXS), the most common cause of inherited intellectual disability, yet it is unknown which brain regions and cell types within them contribute to disease pathophysiology. We used conditional tagging of FMRP and CLIP (cTag FMRP CLIP) to examine FMRP targets specifically in CA1 hippocampal neurons, a critical cell type for learning and memory known to have altered synaptic function in FXS. Integrating this data with analysis of ribosome-bound transcripts from the same neuronal population revealed CA1-enriched binding of autism-relevant mRNAs, and unexpected CA1-specific regulation of transcripts encoding circadian proteins.

2020-01-07 | GSE127846 | GEO

FMRP regulates mRNAs encoding distinct functions in the cell body and dendrites of CA1 pyramidal neurons [PAPERCLIP]

2022-05-11 | GSE180413 | GEO

Opto-CLIP reveals dynamic FMRP regulation of mRNAs upon CA1 neuronal activation [CLIP]

Project description:Opto-CLIP reveals dynamic FMRP regulation of mRNAs upon CA1 neuronal activation [CLIP]

| PRJNA1209012 | ENA

FMRP regulates mRNAs encoding distinct functions in the cell body and dendrites of CA1 pyramidal neurons [TRAP-seq, RNA-seq]

2022-01-19 | GSE174303 | GEO

FMRP cTag CLIP from mouse CA1 pyramidal neurons

Project description:FMRP cTag CLIP from mouse CA1 pyramidal neurons

| PRJNA525639 | ENA

FMRP regulates mRNAs encoding distinct functions in the cell body and dendrites of CA1 pyramidal neurons [FMRP-CLIP]

Project description:FMRP regulates mRNAs encoding distinct functions in the cell body and dendrites of CA1 pyramidal neurons [FMRP-CLIP]

| PRJNA748080 | ENA

The Fragile X Mental Retardation Protein (FMRP) controls diacylglycerol kinase in neurons

Project description:In this study, we sought to identify the mRNAs associated to FMRP protein in mouse cortical neuron using a cross linking immunoprecipitation and microarray (CLIP-microarray). The mRNAs crosslinked at 254 nm to FMRP in mouse cortical neurons cultured 8 days in vitro (8 DIV) were immunoprecipitated with H120 anti-FMRP (Santa Cruz) and reverse transcribed to labeled cDNAs with Ovation Pico WTA system V2 (Nugen) and hybridized on Mouse Gene 1.0ST (Affymetrix) We analyzed total RNA (Input) and FMRP-CLIPed RNA (Clip) from 10 primary cortical neuron mouse cultures (5 Wt Input, 5 FMR1-KO Input, 5 Wt Clip, 5 FMR1-KO Clip). Array data was processed by Affymetrix Exon Array Computational Tool. No technical replicates were performed.

2016-06-01 | E-GEOD-51649 | biostudies-arrayexpress

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