Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Altered nucleocytoplasmic export of adenosine (A)-rich circRNAs by PABPC1 contributes to neuronal function [FB_KD_circRTN4_RNAseq]

ABSTRACT: Circular RNAs (circRNAs) are upregulated during neurogenesis. Where and how circRNAs are localized, and what roles they play during this process have remained elusive. By comparing the nuclear and cytoplasmic circRNAs between H9 cells and H9-derived forebrain neurons (FB), we found a subset of adenosine (A)-rich circRNAs are restricted in H9 nuclei but exported to cytosols upon forebrain neuron differentiation. This differentiation-coupled circRNA subcellular relocation is modulated by the poly(A)-binding protein PABPC1. In the nucleus, newly produced (A)-rich circRNAs are bound by PABPC1 and the nuclear basket protein TPR to prevent their nucleocytoplasmic export. Modulation of (A)-rich motifs in circRNAs remarkably alters their subcellular localization. Enforced (A)-rich circRNAs in cytosols result in mRNA translation suppression. Furthermore, decreased nuclear PABPC1 upon neuronal differentiation enables the export of (A)-rich circRNAs including circRTN4(2,3), which is required for neurite outgrowth. These findings uncover subcellular localization features of circRNAs, linking their processing and function during neurogenesis.

ORGANISM(S): Homo sapiens

PROVIDER: GSE265930 | GEO | 2024/04/30

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Altered nucleocytoplasmic export of adenosine (A)-rich circRNAs by PABPC1 contributes to neuronal function

Project description:Circular RNAs (circRNAs) are upregulated during neurogenesis. Where and how circRNAs are localized, and what roles they play during this process have remained elusive. By comparing the nuclear and cytoplasmic circRNAs between H9 cells and H9-derived forebrain neurons (FB), we found a subset of adenosine (A)-rich circRNAs are restricted in H9 nuclei but exported to cytosols upon forebrain neuron differentiation. This differentiation-coupled circRNA subcellular relocation is modulated by the poly(A)-binding protein PABPC1. In the nucleus, newly produced (A)-rich circRNAs are bound by PABPC1 and the nuclear basket protein TPR to prevent their nucleocytoplasmic export. Modulation of (A)-rich motifs in circRNAs remarkably alters their subcellular localization. Enforced (A)-rich circRNAs in cytosols result in mRNA translation suppression. Furthermore, decreased nuclear PABPC1 upon neuronal differentiation enables the export of (A)-rich circRNAs including circRTN4(2,3), which is required for neurite outgrowth. These findings uncover subcellular localization features of circRNAs, linking their processing and function during neurogenesis.

2024-04-30 | GSE265924 | GEO

Nuclear export of circular RNA

Project description:Circular RNAs (circRNAs), which can function as regulators of gene expression, are formed by back-splicing of precursor mRNAs in the nucleus. circRNAs are predominantly localized in the cytoplasm, indicating that they must be exported from the nucleus. Here, we uncover a pathway specific for nuclear export of circular RNA. This pathway requires Ran-GTP, Exportin-2 and IGF2BP1. Enhancing the nuclear Ran-GTP gradient by depletion or chemical inhibition of the major protein exporter, CRM1, selectively increases nuclear export of circRNAs, while reducing the nuclear Ran-GTP gradient selectively blocks circRNA export. Analysis of nuclear circRNA binding proteins reveals that interaction of IGF2BP1 with circRNA is enhanced by Ran-GTP, whereas its interaction with linear RNA is inhibited by Ran-GTP. Depletion or knockout of Exportin-2 specifically inhibits nuclear export of circRNA, while formation of an Exportin-2 circRNA export complex requires Ran-GTP and IGF2BP1. Our findings demonstrate that adaptors such as IGF2BP1 that bind directly to circular RNAs recruit Exportin-2 to export circRNAs in a mechanism analogous to protein export, rather than mRNA export.

2023-12-09 | GSE235899 | GEO

Nuclear export of circular RNA

Project description:Circular RNAs (circRNAs), which are increasingly being implicated in a variety of functions in normal and cancerous cells1-5, are formed by back-splicing of precursor mRNAs in the nucleus6-10. circRNAs are predom¬inantly localized in the cytoplasm, indicating that they must be exported from the nucleus. Here, we uncover a pathway specific for nuclear export of circular RNA. This pathway requires Ran-GTP, Exportin-2 and IGF2BP1. Enhancing the nuclear Ran-GTP gradient by depletion or chemical inhibition of the major protein exporter, CRM1, selectively increases nuclear export of circRNAs, while reducing the nuclear Ran-GTP gradient selectively blocks circRNA export. Depletion or knockout of Exportin-2 specifically inhibits nuclear export of circRNA. Analysis of nuclear circRNA binding proteins reveals that interaction of IGF2BP1 with circRNA is enhanced by Ran-GTP. Formation of circRNA export complexes in the nucleus is promoted by Ran-GTP through its interactions with IGF2BP1, Exportin-2 and circRNA. Our findings demonstrate that adaptors such as IGF2BP1 that bind directly to circular RNAs recruit Ran-GTP and Exportin-2 to export circRNAs in a mechanism analogous to protein export, rather than mRNA export.

2023-11-22 | GSE226716 | GEO

Subcellular RNA localization during Drosophila embryonic neurogenesis [fractionation-Seq]

Project description:Subcellular RNA localization during Drosophila embryonic neurogenesis [fractionation-Seq]

| PRJNA415601 | ENA

Nuclear retention of fission yeast dicer is a prerequisite for RNAi-mediated heterochromatin assembly

Project description:RNAseIII ribonucleases act at the heart of RNA silencing pathways by processing precursor RNAs into mature microRNAs and siRNAs. In the fission yeast Schizosaccharomyces pombe, siRNAs are generated by the RNAseIII enzyme Dcr1 and are required for heterochromatin formation. In this study, we have analyzed the subcellular localization of Dcr1 and found that it accumulates in the nucleus and is enriched at the nuclear periphery. Nuclear accumulation of Dcr1 depends on a short motif which constrains nuclear export promoted by the double-stranded RNA binding domain of Dcr1. Absence of this motif renders Dcr1 mainly cytoplasmic and is accompanied by remarkable changes in gene expression and failure to assemble heterochromatin. Our findings suggest that dicer proteins are shuttling proteins and that the steady-state subcellular levels can be shifted towards either compartment. This has implications for the mechanism of RNAi-mediated heterochromatin assembly and the spatial organization of RNA silencing pathways in general. Small RNA libraries from total RNA isolations of wild-type, dcr1Delta and dcr1DeltaC33 cells and subjected to high-throughput sequencing.

2010-02-16 | E-GEOD-18582 | biostudies-arrayexpress

Gene architecture and sequence composition underpin selective dependency of long RNAs on components of the nuclear export pathway

Project description:The nuclear export pathway transports long RNAs produced in the nucleus to the cytoplasm. The core components of this pathway are thought to be required for export of virtually all polyadenylated RNAs. Here, we depleted different proteins that act in nuclear export in human cells, and quantified the transcriptome-wide consequences on RNA localization. Different genes exhibited substantially variable sensitivities, with depletion of NXF1 and TREX components causing some transcripts to become strongly retained in the nucleus while others were not affected. Specifically, NXF1 is preferentially required for export of single- or few-exon transcripts with long exons or high A/U-content, whereas depletion of TREX complex components preferentially affects spliced and G/C-rich transcripts. Using massively parallel reporter assays we identified short sequence elements that render transcripts dependent on NXF1 for their export, and identified synergistic effects of splicing and NXF1. These results revise the current model of how nuclear export shapes the distribution of RNA within human cells.

2020-05-25 | GSE139151 | GEO

A complex with poly(A) binding protein cytoplasmic 1 and EWS facilitates oncogenic ETS transcription factor function in prostate cells

Project description:The ETS transcription factor ERG is aberrantly expressed in approximately 50% of prostate tumors due to chromosomal rearrangements such as TMPRSS2/ERG. The ability of ERG to drive oncogenesis in prostate epithelial cells requires interaction with distinct co-activators, such as the RNA-binding protein EWS. Here, we find that ERG has both direct and indirect interactions with EWS, and the indirect interaction is mediated by the poly-A RNA-binding protein PABPC1. PABPC1 directly bound both ERG and EWS. ERG expression in prostate cells promoted PABPC1 localization to the nucleus and recruited PABPC1 to ERG/EWS binding sites in the genome. Knockdown of PABPC1 in prostate cells abrogated ERG-mediated phenotypes and decreased the ability of ERG to activate transcription. These findings define a complex including ERG and the RNA-binding proteins EWS and PABPC1 that represents a novel therapeutic target for ERG-positive prostate cancer and identify a novel nuclear role for PABPC1.

2023-11-06 | GSE226472 | GEO

Atlas of Subcellular RNA Localization Revealed by APEX-seq

Project description:We introduce APEX-seq, a method for RNA sequencing based on direct proximity labeling of RNA using the peroxidase enzyme APEX2. APEX-seq in nine distinct subcellular locales produced a nanometer-resolution spatial map of the human transcriptome as a resource, revealing extensive patterns of localization for diverse RNA classes and transcript isoforms. We uncover a radial organization of the nuclear transcriptome, which is gated at the inner surface of the nuclear pore for cytoplasmic export of processed transcripts. We identify two distinct pathways of messenger RNA localization to mitochondria, each associated with specific sets of transcripts for building complementary macromolecular machines within the organelle. APEX-seq should be widely applicable to many systems, enabling comprehensive investigations of the spatial transcriptome.

2019-06-20 | GSE116008 | GEO

NES_functional_survivin vs NES_mutated_survivin exposed or unexposed to temozolomide (TMZ)

Project description:Investigation of the impact of survivin subcellular localisation on gene expression upon TMZ in glioblastoma cell clones, ectopically expressing either cytoplasmic or nuclear survivin-GFP. In case of nuclear survivin-GFP, survivin is trapped in the nucleus, because the nuclear export sequence (NES) has been mutated

2021-07-14 | GSE154337 | GEO

Characterisation of the temporal hepatic transcriptome at subcellular level

Project description:In eukaryotes, RNA is synthesized in the nucleus, spliced, and exported to the cytoplasm where it is translated and finally degraded. Any of these steps could be subject to temporal regulation during the circadian cycle, generating daily fluctuations of RNA accumulation and impacting the distribution of transcripts in different subcellular compartments. Here, we performed a comprehensive analysis of nuclear and cytoplasmic, polyA and total, transcriptomes of mouse livers sampled along the daily cycle. These data provide a genome-wide temporal inventory of RNA subcellular enrichments, and revealed specific signatures of splicing, nuclear export and cytoplasmic mRNA stability related to transcript and gene lengths. Combined with a mathematical model describing rhythmic RNA profiles , we could test the rhyhtmicity of export rates and cytoplasmic degradation rates of ~1400 genes. While nuclear export times are usually much shorter than cytoplasmic half-lives, we found that that nuclear export contributes to the modulation and generation of rhythmic profiles of ~10% of the cycling nuclear mRNAs. This study provides an estimation of the nuclear and cytoplasmic life times in the liver and contributes to a better understanding of the dynamic regulation of the transcriptome during the feeding-fasting cycle.

2022-06-01 | GSE182856 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

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