Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Loss of the long non-coding RNA, Malat1, accelerates premature aging and mortality

ABSTRACT: Here we show that the 5’ end and 3’ end of Malat1 are dependently and independently expressed. Loss of 5’ Malat1 up-regulates Neat1 in cis, while loss of 3’ Malat1 globally regulated gene expression in trans. Furthermore, loss of 3’ Malat1 accelerates premature aging and shortens the lifespan in mice, but loss of 5’ Malat1 produces no phenotypic changes. Mechanistically, 3’ Malat1 exerts a tight regulation of P21 that is drastically up-regulated in brain and retina upon its deletion in mice. This is very likely mediated at two different levels. One is at the mRNA level since Malat1 interacts with hnRNP A1 and hnRNP A2/B1. This is independently of P53 since it is significantly decreased upon 3’ Malat1 KO, probably due to the down-regulation of hnRNP C which has been shown to maintain P53 mRNA stability in our cell line model. The other is at the protein level through NPM, which is significantly up-regulated in 3’ Malat1 KO and which was known to decrease P21 ubiquitination and hence stabilizing of P21. These observations reveal previously unknown functions of 3’ Malat in the brain and indicates the need for more detailed understanding of highly abundant conserved lncRNAs, such as Malat1, and alarms for detailed understanding before therapeutic targeting in the future.

ORGANISM(S): Mus musculus

PROVIDER: GSE130392 | GEO | 2022/07/02

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Intestinal ablation of CKIalpha highlights invasiveness control

Project description:Wnt signaling, which drives the rapid self-renewal of the gut epithelium is causally associated with intestinal neoplasia. Here we show that CKIalpha is a activation depends on p53 and p21Waf1/Cip1: CKIÎ± ablation provokes activation of p53 and p21, which assume a pivotal role in suppressing invasive cancer. Dual loss of CKIalpha and either p53 or p21 results in rapid, rampant malignant signature denoted p53supinv (p53-suppressed invasiveness) that is conditionally induction of invasiveness. Like invasiveness control, the transcriptional suppression of p53supinv genes is largely mediated by p21, independently of cell cycle control, representing a novel tumor suppressor function of wild-type p53. 13 arrays of mice entrocytes herto or homozygot for gut specific KO of CKI alpha. Crossed with p53 or p21 KO mice.

2010-10-23 | E-GEOD-24760 | biostudies-arrayexpress

Long Noncoding RNA MALAT1 Controls Cell Cycle Progression by Regulating the Expression of Oncogenic Transcription Factor B-MYB

Project description:The long noncoding MALAT1 RNA is upregulated in cancer tissues and its elevated expression is associated with hyper-proliferation, but the underlying mechanism is poorly understood. We demonstrate that MALAT1 levels are regulated during normal cell cycle progression. Genome-wide transcriptome analyses in normal human diploid fibroblasts reveal that MALAT1 modulates the expression of cell cycle genes, and is required for G1/S and mitotic progression. Depletion of MALAT1 leads to activation of p53 and its target genes. The cell cycle defects observed in MALAT1-depleted cells are sensitive to p53 levels, indicating that p53 is a major downstream mediator of MALAT1 activity. Furthermore, MALAT1-depleted cells display reduced expression of B-MYB (Mybl2), an oncogenic transcription factor involved in G2/M progression, due to altered binding of splicing factors on B-MYB pre-mRNA and aberrant alternative splicing. In human cells, MALAT1 promotes cellular proliferation by modulating the expression and/or premRNA processing of cell cycle-regulated transcription factors. These findings provide mechanistic insights on the role of MALAT1 in regulating cellular proliferation. Keywords: MALAT1; MALAT-1, NEAT2, ncRNA; E2F, alternative splicing; pre-mRNA splicing factors WI38 cells (normal human diploid fibroblasts) were transfected with a control oligo (CTR) or antisense oligos to MALAT1 and RNA was isolated after 48 hr. Two antisense oligos were use for MALAT1 (AS-1 and AS-2). Arrays were done for 3 sets of samples in triplicate (control, AS-1 and AS-2).

2014-05-16 | E-GEOD-44240 | biostudies-arrayexpress

The p53-regulated long noncoding RNA, lincRNA-p21 promotes the expression of Polycomb target genes and enforces the G1/S checkpoint by activating p21 in cis [ChIP-seq]

Project description:The p53-regulated long non-coding RNA, lincRNA-p21, has been proposed to promote apoptosis and to repress in trans the expression of genes in the p53 transcriptional network. Here, we report the generation of a conditional knockout mouse model developed to further examine lincRNA-p21 function. Using this genetic approach, we find that the primary function of lincRNA-p21 is to activate in cis the expression of its neighboring gene, the cyclin-dependent kinase inhibitor p21. Mechanistically, we show that lincRNA-p21 acts in concert with hnRNP-K as a co-activator for p53-dependent transcription of p21. Additional phenotypes of lincRNA-p21 deficiency, including deregulated expression and altered chromatin state of a set of Polycomb target genes, defective G1/S checkpoint, increased proliferation rates, and enhanced reprogramming efficiency could be attributed to diminished p21 levels. This study reveals a novel paradigm, whereby the long non-coding RNA lincRNA-p21 affects global gene expression and influences events in the p53 tumor suppressor pathway by acting in cis as a locus-restricted transcriptional co-activator for p53-mediated expression of p21. Examination of 2 different histone modifications (H3K4me3 and H3K27me3) in 2 cell types (WT and lincRNA-p21 KO) in the presence and absence of Doxorubicin.

2014-05-22 | E-GEOD-52956 | biostudies-arrayexpress

The p53-regulated long noncoding RNA, lincRNA-p21 promotes the expression of Polycomb target genes and enforces the G1/S checkpoint by activating p21 in cis [RNA-seq]

Project description:The p53-regulated long non-coding RNA, lincRNA-p21, has been proposed to promote apoptosis and to repress in trans the expression of genes in the p53 transcriptional network. Here, we report the generation of a conditional knockout mouse model developed to further examine lincRNA-p21 function. Using this genetic approach, we find that the primary function of lincRNA-p21 is to activate in cis the expression of its neighboring gene, the cyclin-dependent kinase inhibitor p21. Mechanistically, we show that lincRNA-p21 acts in concert with hnRNP-K as a co-activator for p53-dependent transcription of p21. Additional phenotypes of lincRNA-p21 deficiency, including deregulated expression and altered chromatin state of a set of Polycomb target genes, defective G1/S checkpoint, increased proliferation rates, and enhanced reprogramming efficiency could be attributed to diminished p21 levels. This study reveals a novel paradigm, whereby the long non-coding RNA lincRNA-p21 affects global gene expression and influences events in the p53 tumor suppressor pathway by acting in cis as a locus-restricted transcriptional co-activator for p53-mediated expression of p21. mRNAseq in 2 cell types (WT and lincRNA-p21 KO) in the presence and absence of Doxorubicin performed in biological triplicate.

2014-05-22 | E-GEOD-52957 | biostudies-arrayexpress

Long Noncoding RNA MALAT1 Controls Cell Cycle Progression by Regulating the Expression of Oncogenic Transcription Factor B-MYB

2014-05-16 | GSE44240 | GEO

A large intergenic non-coding RNA induced by p53 mediates global gene repression in the p53 transcriptional response

Project description:Recently, more than a thousand large intergenic non-coding RNAs (lincRNAs) have been reported. These RNAs are evolutionarily conserved in mammalian genomes and thus presumably function in diverse biological processes. Here, we report the identification of lincRNAs that are regulated by p53. One of these lincRNAs (lincRNA-p21) serves as a repressor in p53-dependent transcriptional responses. Inhibition of lincRNA-p21 affects the expression of hundreds of gene targets enriched for genes normally repressed by p53. The observed transcriptional repression by lincRNA-p21 is mediated through the physical association with hnRNP-K. This interaction is required for proper genomic localization of hnRNP-K at repressed genes and regulation of p53 mediated apoptosis. We propose a model whereby transcription factors activate lincRNAs that serve as key repressors by physically associating with repressive complexes and modulating their localization to sets of previously active genes.

2010-08-09 | GSE21761 | GEO

Intestinal ablation of CKIalpha highlights invasiveness control

Project description:Wnt signaling, which drives the rapid self-renewal of the gut epithelium is causally associated with intestinal neoplasia. Here we show that CKIalpha is a activation depends on p53 and p21Waf1/Cip1: CKIα ablation provokes activation of p53 and p21, which assume a pivotal role in suppressing invasive cancer. Dual loss of CKIalpha and either p53 or p21 results in rapid, rampant malignant signature denoted p53supinv (p53-suppressed invasiveness) that is conditionally induction of invasiveness. Like invasiveness control, the transcriptional suppression of p53supinv genes is largely mediated by p21, independently of cell cycle control, representing a novel tumor suppressor function of wild-type p53.

2010-10-23 | GSE24760 | GEO

The p53-regulated long noncoding RNA, lincRNA-p21 promotes the expression of Polycomb target genes and enforces the G1/S checkpoint by activating p21 in cis [RNA-seq]

2014-05-22 | GSE52957 | GEO

The p53-regulated long noncoding RNA, lincRNA-p21 promotes the expression of Polycomb target genes and enforces the G1/S checkpoint by activating p21 in cis [ChIP-seq]

2014-05-22 | GSE52956 | GEO

LincRNA-p21 Blocks Somatic Cell Reprogramming by Sustaining H3K9me3 and CpG Methylation at Pluripotent Gene Promoters

Project description:Through expression profiling and functional screening we have identified the large intergenic non-coding RNA p21 (lincRNA-p21) as a barrier for reprogramming. LincRNA-p21 is induced by p53 but contrary to its role in the DNA damage response it does not promote apoptosis or cell senescence in reprogramming. Instead, lincRNA-p21 associates with the H3K9 methyltransferase Setdb1 and the maintenance DNA methyltransferase Dnmt1 in separate complexes that are facilitated by the RNA binding protein hnRNP-K.

2014-12-29 | GSE57967 | 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