Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Total and dendritic ribosome profiling from primary mouse cortical neurons

ABSTRACT: Activity-dependent protein synthesis is critical for determining changes in dendritic proteomes underlying brain function, yet the mechanisms governing these changes are lacking. Here, we combined proximity-based labeling of dendritic transcriptome, translatome, and proteome to study the dynamics of RNA regulation in activated synapses. We discovered that depolarization leads to a switch from RNAs translated under basal conditions to new translation of previously unrecognized subsets of depolarization-dependent transcripts. Dynamically regulated RNAs bound by specific regulatory proteins, including NOVA1, FMRP, and ELAVLs, rapidly generate proteins with roles in mitochondrial regulation, RNA metabolism, translational control, and synaptic signaling in dendrites. Knockdowns of activity-induced dendritic RNAs altered neuronal physiology, underscoring how dynamic switches in the regulation of RNAs encoding coordinated sets of proteins underlie synaptic plasticity.

ORGANISM(S): Mus musculus

PROVIDER: GSE213023 | GEO | 2024/03/14

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Total and dendritic RNA-sequencing from primary mouse cortical neurons

Project description:Activity-dependent protein synthesis is critical for determining changes in dendritic proteomes underlying brain function, yet the mechanisms governing these changes are lacking. Here, we combined proximity-based labeling of dendritic transcriptome, translatome, and proteome to study the dynamics of RNA regulation in activated synapses. We discovered that depolarization leads to a switch from RNAs translated under basal conditions to new translation of previously unrecognized subsets of depolarization-dependent transcripts. Dynamically regulated RNAs bound by specific regulatory proteins, including NOVA1, FMRP, and ELAVLs, rapidly generate proteins with roles in mitochondrial regulation, RNA metabolism, translational control, and synaptic signaling in dendrites. Knockdowns of activity-induced dendritic RNAs altered neuronal physiology, underscoring how dynamic switches in the regulation of RNAs encoding coordinated sets of proteins underlie synaptic plasticity.

2024-03-14 | GSE213012 | GEO

eIF4G2 cross-linking immunoprecipitation (CLIP) in primary cortical neurons

Project description:Learning and memory require activity-induced changes in mRNA translation within dendrites, but which mRNAs are involved and how they are regulated remain unclear. We combined proximity labeling with ribosome profiling and CLIP to monitor how depolarization impacts dendritic translation. For a functionally coherent set of transcripts highly enriched in mitochondrial genes, depolarization leads to enhanced uORF translation, eIF4G2 binding, and increased translation. Engineered reporters demonstrate that activity-dependent translational control is conferred by the 5’UTRs and that dendritic localization, eIF4G2 binding, and uORF translation are necessary and sufficient to mediate this regulation. Downstream, this drives activity-dependent changes in dendritic mitochondrial function. Our studies uncover an unanticipated mechanism by which activity-dependent uORF translational control by eIF4G2 enables the coupling of synaptic activity to local remodeling of dendrites.

2024-03-14 | GSE213082 | GEO

ORFRATER analysis of ribosome profiling data from primary mouse cortical neurons

2024-03-14 | GSE213008 | GEO

Microarray analyses that reveal the population of dendritic RNAs and their redistribution by neural activity

Project description:Subcellular localization of RNA is an efficient way to localize proteins to a specific region of a cell. The dendritic localization of RNAs underlies the establishment and maintenance of the synaptic functions of neuronal cells. A requirement for dendritic RNA localization and subsequent local translation has been demonstrated in several forms of experience-dependent synaptic plasticity. In spite of several attempts to identify these RNAs, the population of RNA species present in dendrites as a whole has not been well described. Here we show the results of microarray analyses with RNAs isolated from heavy portion of polysome (HP) fraction where RNA granules are enriched in and synaptosome fraction, prepared from the rat brain. These analyses revealed the complex nature of the dendritic RNA population, which included RNAs that were not expected to be in the dendrites. Neural activity caused by an electroconvulsive shock triggered a redistribution of the population of dendritic transcriptome towards the area of overlap between the HP and the synaptosome, which is assumed to be neck of spine. This redistribution may accompany some changes in the translatability of those transcriptome, which suggests complex mechanisms of local translation in response to synaptic inputs. Keywords: Comparisons of RNAs that are presumed to be derived from neuronal dendritic parts (HP and D4) with those from somas (LP and C2).

2007-02-06 | GSE6499 | GEO

Functionally diverse dendritic mRNAs rapidly associate with ribosomes following a novel experience

Project description:The subcellular localization and translation of messenger RNA (mRNA) supports functional differentiation between cellular compartments. In neuronal dendrites, local translation of mRNA provides a rapid and specific mechanism for synaptic plasticity and memory formation, and might be involved in the pathophysiology of certain brain disorders. Despite the importance of dendritic mRNA translation, little is known about which mRNAs can be translated in dendrites in vivo and when their translation occurs. Here we collect ribosome-bound mRNA from the dendrites of CA1 pyramidal neurons in the adult mouse hippocampus. We find that dendritic mRNA rapidly associates with ribosomes following a novel experience consisting of a contextual fear conditioning trial. High throughput RNA sequencing followed by machine learning classification reveals an unexpected breadth of ribosome-bound dendritic mRNAs, including mRNAs expected to be entirely somatic. Our findings are in agreement with a mechanism of synaptic plasticity that engages the acute local translation of functionally diverse dendritic mRNAs. RNA-Seq of ribosome-bound mRNA immunoprecipitated from dendrites and soma of CA1 pyramidal neurons in the mouse hippocampus

2014-07-30 | E-GEOD-58343 | biostudies-arrayexpress

Transcription profiling of rat synaptosomes of the hippocampus vs. total hippocampus reveals activity- and mTOR-dependent suppression of Kv1.1 channel mRNA translation in dendrites

Project description:Mammalian target of rapamycin (mTOR) is implicated in synaptic plasticity and local translation in dendrites. Here we found that the mTOR inhibitor, rapamycin, increased the Kv1.1 voltage-gated potassium channel protein in hippocampal neurons and promoted Kv1.1 surface expression on dendrites without altering its axonal expression. Moreover, endogenous Kv1.1 mRNA was detected in dendrites. Using Kv1.1 fused to the photo-convertible fluorescence protein Kaede as a reporter for local synthesis, we observed Kv1.1 synthesis in dendrites upon inhibition of mTOR or the N-methyl-D-aspartate (NMDA) glutamate receptor. Thus, synaptic excitation may cause local suppression of dendritic Kv1 channels by reducing their local synthesis. Experiment Overall Design: mRNA isoloated from the synaptosomes of the hippocampus is compared to mRNA isolated from the total hippocampus to identify mRNAs that are enriched at the synapse

2008-06-13 | E-GEOD-5516 | biostudies-arrayexpress

Hippocampal Subregions Express Distinct Dendritic Transcriptomes that Reveal Differences in Mitochondrial Function in CA2 [RNA-seq]

Project description:RNA localization is one mechanism that neurons use to spatially and temporally regulate gene expression at synapses. Here, we tested the hypothesis that cells exhibiting distinct forms of synaptic plasticity will have differences in dendritically localized RNAs. Indeed, we discovered that each major subregion of the adult mouse hippocampus expresses a unique complement of dendritic RNAs. Specifically, we uncovered a surprising number of cell type and compartment specific differences in RNA expression and alternative splicing, some of which pointed to differences within interneuron and non-neuronal cells present in dendritic laminae. Further, by focusing gene-ontology analyses on the plasticity-resistant CA2, we identified an enrichment of mitochondria-associated pathways in CA2 cell bodies and dendrites, and we provide functional evidence that these pathways influence plasticity and mitochondrial respiration in CA2. In sum, our results support accumulating evidence that thousands of RNAs are present in adult dendrites that likely function to regulate cell type specific processes in dendrites.

2019-09-23 | GSE116342 | GEO

Hippocampal Subregions Express Distinct Dendritic Transcriptomes that Reveal Differences in Mitochondrial Function in CA2 [array]

2019-09-23 | GSE116328 | GEO

FMRP phosphorylation modulates neuronal translation through YTHDF1

Project description:Translation activation of local synaptic mRNA is critical to learning and memory. Despite extensive studies on how phosphorylations of ribosome units and translation factors enable fast response to exogenous stimuli, our knowledge on molecular pathways utilized by RNA binding proteins (RBPs) to control translation of specific mRNAs remains incomplete. We have previously found that YTHDF1 regulates depolarization-induced protein synthesis by promoting translation of N6-methyladenosine (m6A)-modified transcripts. Here we report an unexpected mechanism that the stimuli-induced neuronal translation is mediated by phosphorylation of a YTHDF1-binding protein FMRP. Phosphorylation of FMRP serine 499 induced by neuronal depolarization alters the condensing behavior of prion-like protein YTHDF1. Unphosphorylated FMRP sequesters YTHDF1 away from the translation initiation complex, whereas the stimulation-induced FMRP phosphorylation releases YTHDF1 to form translational active condensates with the ribosome to activate translation of YTHDF1 target transcripts. In fragile X syndrome (FXS) models characterized with low FMRP expression, we observed YTHDF1-mediated hyperactive translation, which notably impacts FXS pathophysiology. Developmental defects in an FXS forebrain organoid model could be reversed by a selective small-molecule inhibitor of YTHDF1 which acts by suppressing its condensation in neurons. We characterized transcriptome-wide translation alterations with the inhibitor treatment in organoids and identified targets that explain alleviated FXS pathology. Our study thus reveals FMRP and its phosphorylation as an important regulator of the activity-dependent translation during neuronal development and stimulation, and identifies YTHDF1 as a potential therapeutic target for FXS in which developmental defects caused by FMRP depletion could be reversed through YTHDF1 inhibition.

2023-10-31 | GSE214882 | GEO

Neural circular RNAs are derived from synaptic genes and regulated by development and plasticity

Project description:Circular RNAs (circRNAs), formed by the atypical head-to-tail splicing of exons, have re-emerged as a potentially interesting RNA species given recent reports of a surprising diversity and abundance of circRNA in organisms ranging from worm to human. Here, using deep RNA sequencing, we profiled different RNA species in mouse and observed that circRNAs are significantly enriched in neural tissue, relative to other tissues. Using PacBio sequencing, we determined, for the first time, the circular structure of this population of circRNAs as well as their full-length sequences. We discovered that a disproportionate fraction of the brain circRNA population is derived from host genes that code for synaptic proteins. Moreover, based on the separate profiling of the RNAs localized in neuronal cell bodies and neuropil (enriched in axons and dendrites), we found that, on average, circular RNAs are more enriched in the neuropil than their host gene mRNA isoforms. Using high resolution in situ hybridization we, for the first time, directly visualized circRNA punctae in the dendrites of neurons. The host gene origin and location of the circRNA in neurons suggest the possibility that circRNAs might participate in the regulation of synaptic function and plasticity. Consistent with this idea, we observed via profiling at different developmental stages, that the abundance of many circular RNAs changes abruptly at a time corresponding to synaptogenesis. In addition, following a homeostatic downscaling of neuronal activity many circRNAs exhibit significant up or down-regulation. These data indicate that brain circRNAs are positioned to respond to and regulate synaptic function. Circular RNA profiling in 13 different samples in mice and four samples in rat, using Illumina sequencing

2015-02-25 | E-GEOD-61991 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data