Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Partial loss of CFIm25 causes aberrant alternative polyadenylation and learning deficits [mouse]

ABSTRACT: Partial loss of CFIm25 causes aberrant alternative polyadenylation and learning deficits [mouse]

PROVIDER: PRJNA597918 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR10798638.fastq.gz	Fastqsanger.gz
	SRR10798639.fastq.gz	Fastqsanger.gz
	SRR10798640.fastq.gz	Fastqsanger.gz
	SRR10798641.fastq.gz	Fastqsanger.gz
	SRR10798642.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 6

Similar Datasets

Partial loss of CFIm25 causes aberrant alternative polyadenylation and learning deficits

Project description:We previously showed that NUDT21-spanning copy-number variations (CNVs) are associated with intellectual disability (ID), and that NUDT21-encoded CFIm25 regulates the protein levels of at least one dose-sensitive, ID-associated protein: MeCP2 (Gennarino et al., 2015). However, the patients’ CNVs also spanned multiple other genes raising the possibility that loss or gain of these other genes caused their symptoms. To determine if reduced NUDT21 function alone is sufficient to cause disease, we generated Nudt21 heterozygous null mice to mimic the human state of reduced expression. We found that although these mice have 50% reduced Nudt21 mRNA, they only have 30% less of its cognate protein, CFIm25. Despite this partial protein-level compensation, the Nudt21+/- mice have learning deficits and cortical hyperexcitability. Further, to determine the molecular mechanism driving neural dysfunction, we partially inhibited NUDT21 in human embryonic stem cell-derived neurons to reduce CFIm25 by 30%. This reduction in CFIm25 was sufficient to induce misregulated alternative polyadenylation (APA) and protein levels in hundreds of genes, dozens of which are associated with intellectual disability and whose dysregulation is likely contributing to disease symptoms. Altogether, these results indicate that disruption of NUDT21-regulated APA events in the brain can cause intellectual disability.

2019-08-14 | PXD014842 | Pride

Partial loss of CFIm25 causes aberrant alternative polyadenylation and learning deficits

2020-04-27 | GSE135384 | GEO

Partial loss of CFIm25 causes aberrant alternative polyadenylation and learning deficits [mouse]

2020-04-15 | GSE142681 | GEO

Partial loss of CFIm25 causes aberrant alternative polyadenylation and learning deficits [human]

2020-04-15 | GSE142682 | GEO

Partial loss of CFIm25 causes aberrant alternative polyadenylation and learning deficits

Project description:Partial loss of CFIm25 causes aberrant alternative polyadenylation and learning deficits

| PRJNA558698 | ENA

Partial loss of CFIm25 causes aberrant alternative polyadenylation and learning deficits [human]

Project description:Partial loss of CFIm25 causes aberrant alternative polyadenylation and learning deficits [human]

| PRJNA597919 | ENA

Partial loss of CFIm25 causes aberrant alternative polyadenylation and learning deficits [superseries]

Project description:Partial loss of CFIm25 causes aberrant alternative polyadenylation and learning deficits [superseries]

| PRJNA597916 | ENA

Partial loss of CFIm25 causes learning deficits and aberrant neuronal alternative polyadenylation.

Project description:We previously showed that NUDT21-spanning copy-number variations (CNVs) are associated with intellectual disability (Gennarino et al., 2015). However, the patients' CNVs also included other genes. To determine if reduced NUDT21 function alone can cause disease, we generated Nudt21+/- mice to mimic NUDT21-deletion patients. We found that although these mice have 50% reduced Nudt21 mRNA, they only have 30% less of its cognate protein, CFIm25. Despite this partial protein-level compensation, the Nudt21+/- mice have learning deficits, cortical hyperexcitability, and misregulated alternative polyadenylation (APA) in their hippocampi. Further, to determine the mediators driving neural dysfunction in humans, we partially inhibited NUDT21 in human stem cell-derived neurons to reduce CFIm25 by 30%. This induced APA and protein level misregulation in hundreds of genes, a number of which cause intellectual disability when mutated. Altogether, these results show that disruption of NUDT21-regulated APA events in the brain can cause intellectual disability.

| S-EPMC7176433 | biostudies-literature

Partial loss of CFIm25 causes aberrant alternative polyadenylation and learning deficits [superseries]

Project description:This SuperSeries is composed of the SubSeries listed below.

2020-04-15 | GSE142683 | GEO

Downregulation of CFIm25 amplifies dermal fibrosis through Alternative Polyadenylation

Project description:Systemic sclerosis (SSc - scleroderma) is a multi-system, fibrotic disease affecting skin and internal organs. Alternative polyadenylation (APA) involves the differential usage of polyadenylation signals, which gives rise to transcripts with variable 3'UTR length. The mammalian Cleavage factor I 25kDa subunit (CFIm25, encoded by NUDT21) is a key regulator of alternative polyadenylation APA and its depletion causes predominantly 3'UTR shortening through loss of stimulation of distal polyA sites resulting in increased used of proximal polyA sites. A shortened 3'UTR will often lack microRNA target sites, resulting in increased mRNA translation due to evasion of microRNA-mediated gene repression. Herein, we report that CFlm25 is downregulated in SSc skin, and primary dermal fibroblasts, andas well as in two murine models of dermal fibrosis.The purpose of this experiment is to identify the APA targets of CFIm25 in human skin fibroblasts. Following the knockdown of CFIm25 in normal human skin fibroblasts, we identified 971 genes with shortened 3’UTRs, including those involved in the transforming growth factor-beta signaling pathway.

2019-09-11 | GSE137276 | 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