Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

LSM12-EPAC1 Defines a Neuroprotective Pathway that Sustains the Nucleocytoplasmic RAN Gradient

ABSTRACT: LSM12-EPAC1 Defines a Neuroprotective Pathway that Sustains the Nucleocytoplasmic RAN Gradient

PROVIDER: PRJNA672153 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR12908227_1.fastq.gz	Fastqsanger.gz
	SRR12908227_2.fastq.gz	Fastqsanger.gz
	SRR12908228_1.fastq.gz	Fastqsanger.gz
	SRR12908228_2.fastq.gz	Fastqsanger.gz
	SRR12908229_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 16

Similar Datasets

LSM12-EPAC1 defines a neuroprotective pathway that sustains the nucleocytoplasmic RAN gradient.

Project description:Nucleocytoplasmic transport (NCT) defects have been implicated in neurodegenerative diseases such as C9ORF72-associated amyotrophic lateral sclerosis and frontotemporal dementia (C9-ALS/FTD). Here, we identify a neuroprotective pathway of like-Sm protein 12 (LSM12) and exchange protein directly activated by cyclic AMP 1 (EPAC1) that sustains the nucleocytoplasmic RAN gradient and thereby suppresses NCT dysfunction by the C9ORF72-derived poly(glycine-arginine) protein. LSM12 depletion in human neuroblastoma cells aggravated poly(GR)-induced impairment of NCT and nuclear integrity while promoting the nuclear accumulation of poly(GR) granules. In fact, LSM12 posttranscriptionally up-regulated EPAC1 expression, whereas EPAC1 overexpression rescued the RAN gradient and NCT defects in LSM12-deleted cells. C9-ALS patient-derived neurons differentiated from induced pluripotent stem cells (C9-ALS iPSNs) displayed low expression of LSM12 and EPAC1. Lentiviral overexpression of LSM12 or EPAC1 indeed restored the RAN gradient, mitigated the pathogenic mislocalization of TDP-43, and suppressed caspase-3 activation for apoptosis in C9-ALS iPSNs. EPAC1 depletion biochemically dissociated RAN-importin β1 from the cytoplasmic nuclear pore complex, thereby dissipating the nucleocytoplasmic RAN gradient essential for NCT. These findings define the LSM12-EPAC1 pathway as an important suppressor of the NCT-related pathologies in C9-ALS/FTD.

| S-EPMC7757817 | biostudies-literature

LSM12-EPAC1 Defines a Neuroprotective Pathway that Sustains the Nucleocytoplasmic RAN Gradient

Project description:We performed gene expression analyses using total RNA-seq and TRAP-seq

2020-11-12 | GSE160159 | GEO

RNA-seq analysis of dark-induced senescence of the leaves of Ran-GDP and Ran-GTP overexpression transgenic plants

Project description:Comparing transcriptome of the leaves of Ran-GDP and Ran-GTP overexpression transgenic plants before and after dark incubation, we discovered 851 differentially expressed genes that designated as Ran-regulated genes. The RNA-seq result confirmed the early senescence phenotype of Ran-GTP overexpression plants and the up-regulation of several signaling pathways, implied their positive roles in Ran-regulated senescence and suggest potential downstream targets of Ran. This study provided a mechanism that senescence process could be regulated by nuclear transportation machinery in Arabidopsis.

2021-04-27 | GSE173375 | GEO

RAN directly binds and stabilizes G3BP1 mRNA in the nucleus to facilitate proliferation and metastasis of nasopharyngeal carcinoma (anti-RAN RIP-seq)

Project description:RNA binding proteins (RBPs) play a critical role in tumor progression by participating in the post-transcriptional regulation of RNA. However, the expression and function of RBPs in nasopharyngeal carcinoma (NPC) remain elusive. This study identified 5 RBPs (RAN, EZH2, RDM1, HRSP12, and ALYREF) that were up-regulated in NPC and could promote NPC cells migration or proliferation. RAN was first investigated because of its most significant effect on NPC cells. Functionally, RAN facilitated NPC proliferation, migration, and invasion in vitro and in vivo. High expression of RAN was associated with poor prognosis of NPC patients and could be performed as a prognostic biomarker. Mechanistically, RAN mediated the nucleus import of TDP43 and enhanced TDP43 nuclear distribution. On the other hand, RAN was directly bound to the coding sequence of G3BP1 mRNA and served as an adapter to facilitate TDP43 interacting with G3BP1 mRNA 3’untranslated region. Thereby increased G3BP1 mRNA stability in the nucleus and led to up-regulation of G3BP1, which further enhanced ATK/ERK phosphorylation and ultimately promoted NPC proliferation and metastasis.

2024-10-31 | GSE262031 | GEO

RAN directly binds and stabilizes G3BP1 mRNA in the nucleus to facilitate proliferation and metastasis of nasopharyngeal carcinoma (si-RAN RNA-seq)

2024-10-31 | GSE262034 | GEO

Lack of RAN-mediated toxicity in Huntington’s disease knock-in mice

Project description:Identification of repeat-associated non-AUG (RAN) translation in trinucleotide (CAG) repeat diseases leads to an emerging concept that CAG repeat diseases are caused by non-polyglutamine products. Nonetheless, the exact contribution of RAN translation to the pathogenesis of CAG repeat diseases remains elusive. Via CRISPR/Cas9-mediated genome editing, we established new knock-in mouse models that harbor expanded CAG repeats in the mouse huntingtin gene, which express RAN translated products or polyglutamine products respectively. Here we report that RAN translation is not detected in the knock-in mouse models, and that only the expanded polyglutamine products can cause neuropathology and behavioral phenotypes. Therefore, polyglutamine products, rather than RAN translated products, play a major role in the pathogenesis of CAG repeat diseases.

2020-02-03 | GSE142603 | GEO

Nucleocytoplasmic mRNA redistribution in ALS motor neurons and is reversed by VCP ATPase inhibition

Project description:Although the pathological hallmark of amyotrophic lateral sclerosis (ALS) is the nucleocytoplasmic mislocalisation of RNA binding proteins (RBPs), such as TDP-43 and FUS, the nucleocytoplasmic distribution of mRNA remains uncharacterised. Here, we used subcellular fractionation with RNA sequencing to assess nucleocytoplasmic mRNA localisation in human induced pluripotent stem cell-derived motor neurons (iPSNs) from ALS patients with TARDBP mutations, VCP mutations, and controls with VCP mutations isogenically knocked in with CRISPR/Cas9. In each mutant group, we found substantial nucleocytoplasmic mRNA redistribution, particularly in transcripts involved in protein binding. Redistributed transcripts in ALS iPSNs were enriched in protein-coding biotypes, exhibited longer lengths, and had enhanced interactions with RBPs, including TDP-43 and FUS. Treatment with the VCP D2 ATPase domain inhibitor ML240 partially restored nucleocytoplasmic mRNA redistribution not only in VCP mutants but also in TARDBP mutant iPSNs.

2023-07-21 | GSE214017 | GEO

RAN directly binds and stabilizes G3BP1 mRNA in the nucleus to facilitate proliferation and metastasis of nasopharyngeal carcinoma (si-G3BP1 RNA-seq)

2024-10-31 | GSE262032 | GEO

A picornavirus protein interacts with Ran-GTPase and disrupts nucleocytoplasmic transport.

Project description:Active nucleocytoplasmic transport of protein and RNA in eukaryotes depends on the Ran-GTPase system to regulate cargo-receptor interactions. Several viruses, including the RNA picornaviruses, encode factors that alter nuclear transport with the aim of suppressing synthesis of antiviral factors and promoting viral replication. Picornaviruses in the cardiovirus genus express a unique 67-aa Leader protein (L), known to alter the subcellular distribution of IFN regulatory proteins targeted to the nucleus. We report here that L binds directly to Ran and blocks nuclear export of new mRNAs. In Xenopus egg extracts, recombinant L also inhibits mitotic spindle assembly, a RanGTP function crucial to cell-cycle progression. We propose that L inhibits nucleocytoplasmic transport during infection by disrupting the RanGDP/GTP gradient. This inhibition triggers an efflux of nuclear proteins necessary for viral replication and causes IFN suppression. To our knowledge, L is the first viral picornaviral protein to interact directly with Ran and modulate the Ran-dependent nucleocytoplasmic pathway.

| S-EPMC1567894 | biostudies-literature

A Molecular Switch for Neuroprotective Astrocyte Reactivity

Project description:Astrocytes differentiate into a spectrum of neurotoxic and neuroprotective reactive subpopulations after CNS injury and in disease. In astrocyte conditional ADCY10 (sAC) knockout mice, reactive astrocytes exhibit a shift towards neurotoxic phenotypes implicating sAC as a critical regulator of neuroprotective astrocyte differentiation.

2023-12-11 | GSE237675 | GEO

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