Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Transcriptomic analysis reveals regulation of adipogenesis via long non-coding RNA, alternative splicing, and alternative polyadenylation

ABSTRACT: Obesity is characterized by dysregulated adipogenesis leading to increased number and/or size of adipocytes. Understanding the molecular mechanisms governing regulation of adipogenesis is therefore key to designing therapeutic interventions against obesity. In our study, we analyzed 3’-end sequencing data generated from sequencing of human preadipocytes and adipocytes, as well as data available in publicly available databases, to propose mechanisms of molecular regulation of adipogenesis. We discovered lncRNAs that have not been previously characterized but may be key regulators of both brown and white adipogenesis. We also demonstrated possible mechanisms of direct or indirect regulation of adipogenesis through alternative splicing. Finally, we show that usage of alternative polyadenylation sites of key adipogenesis genes leads to isoform diversity, which can have significant biological consequences on differentiation efficiency. Therefore, our research reveals potential therapeutic avenues for obesity through manipulation of long non-coding RNA levels, alternative splicing as well as the usage of alternative polyadenylation sites.

ORGANISM(S): Homo sapiens

PROVIDER: GSE250525 | GEO | 2024/08/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Coupling between alternative polyadenylation and alternative splicing is limited to terminal introns

Project description:Alternative polyadenylation has been implicated as an important regulator of gene expression. In some cases, alternative polyadenylation is known to couple with alternative splicing to influence last intron removal. However, it is unknown whether alternative polyadenylation events influence alternative splicing decisions at upstream exons. Knockdown of the polyadenylation factors CFIm25 or CstF64 was used as an approach in identifying alternative polyadenylation and alternative splicing events on a genome-wide scale. Although hundreds of alternative splicing events were found to be differentially spliced in the knockdown of CstF64, genes associated with alternative polyadenylation did not exhibit an increased incidence of alternative splicing. These results demonstrate that the coupling between alternative polyadenylation and alternative splicing is usually limited to defining the last exon. The striking influence of CstF64 knockdown on alternative splicing can be explained through its effects on UTR selection of known splicing regulators such as hnRNP A2/B1, thereby indirectly influencing splice site selection. We conclude that changes in the expression of the polyadenylation factor CstF64 influences alternative splicing through indirect effects. HeLa cell line was stably transfected with shRNA plasmids targeting CstF64. Total RNA was isolated from CstF64 KD cells and wild-type control cells using Trizol according to manufacturerâs protocols. Samples were deep sequenced in duplicate using the Illumina GAIIx system.

2016-03-14 | E-GEOD-79157 | biostudies-arrayexpress

Coupling between alternative polyadenylation and alternative splicing is limited to terminal introns

2016-03-14 | GSE79157 | GEO

Identification of allele-specific alternative mRNA processing via transcriptome sequencing

Project description:Establishing the functional roles of genetic variants remains a significant challenge in the post-genomic era. Here, we present a method, allele-specific alternative mRNA processing (ASARP), to identify genetically influenced mRNA processing events using transcriptome sequencing (RNA-Seq) data. The method examines RNA-Seq data at both single nucleotide and whole-gene/isoform levels to identify allele-specific expression (ASE) and existence of allele-specific regulation of mRNA processing. We applied the methods to data obtained from the human glioblastoma cell line U87MG and primary breast cancer tissues and found that 26M-bM-^@M-^S45% of all genes with sufficient read coverage demonstrated ASE, with significant overlap between the two cell types. Our methods predicted potential mechanisms underlying ASE due to regulations affecting either whole-gene-level expression or alternative mRNA processing, including alternative splicing, alternative polyadenylation and alternative transcriptional initiation. Allele-specific alternative splicing and alternative polyadenylation may explain ASE in hundreds of genes in each cell type. Reporter studies following these predictions identified the causal single nucleotide variants (SNVs) for several allele-specific alternative splicing events. Finally, many genes identified in our study were also reported as disease/phenotype-associated genes in genome-wide association studies. Future applications of our approach may provide ample insights for a better understanding of the genetic basis of gene regulation underlying phenotypic diversity and disease mechanisms. Examine allele-specific gene expression and alternative RNA processing in U87MG cell line

2012-03-29 | E-GEOD-29738 | biostudies-arrayexpress

3T3-L1

Project description:Obesity is an energy balance disorder in which nutrient intake chronically exceeds energy expenditure, resulting in the accumulation of white adipose tissue. Increased adiposity is due to increases in the number and size of adipocytes, which leads to increased body fat and metabolic consequences. Adipocytes induce insulin resistance by promoting lipotoxicity and modulating adipokine secretion. Therefore, a thorough understanding of the mechanisms that regulate adipogenesis could have clinical relevance in preventing and treating obesity and the metabolic syndrome. In this study, we performed miRNA array to measure miRNA profiles of undifferentiated and differentiated 3T3-L1 adipocytes using Agilent(r) miRNA array. We show that miRNA profile changes during adipogenesis. Thus, this data would be useful to find the distinct role of miRNAs for the regulation of adipogenesis.

2013-08-07 | E-MTAB-1783 | biostudies-arrayexpress

Gene-chip studies of adipogenesis-regulated microRNAs in mouse primary adipocytes and human obesity

Project description:This SuperSeries is composed of the following subset Series: GSE27912: Gene-chip studies of adipogenesis-regulated microRNAs in mouse primary adipocytes and human obesity (Exiqon) GSE27949: Gene-chip studies of adipogenesis-regulated microRNAs in mouse primary adipocytes and human obesity (Affymetrix) Refer to individual Series

2011-06-10 | E-GEOD-27951 | biostudies-arrayexpress

Circadian clock regulation of alternative splicing and alternative polyadenylation in Arabidopsis thaliana

Project description:Circadian clock regulation of alternative splicing and alternative polyadenylation in Arabidopsis thaliana

| PRJNA566413 | ENA

Dysregulated RNA polyadenylation contributes to metabolic impairment in non-alcoholic fatty liver disease

Project description:Pre-mRNA processing is an essential mechanism for the generation of mature mRNA and the regulation of gene expression in eukaryotic cells. While defects in pre-mRNA processing have been implicated in a number of diseases their involvement in metabolic pathologies is still unclear. Here we show that both alternative splicing and alternative polyadenylation, two major steps in pre-mRNA processing, are significantly altered in non-alcoholic fatty liver disease (NAFLD). Moreover, we find that Serine and Arginine Rich Splicing Factor 10 (SRSF10) binding is enriched adjacent to consensus polyadenylation motifs and its expression is significantly decreased in NAFLD, suggesting a role mediating pre-mRNA dysregulation in this condition. Consistently, inactivation of SRSF10 in mouse and human hepatocytes in vitro, and in mouse liver in vivo, was found to dysregulate polyadenylation of key metabolic genes such as peroxisome proliferatoractivated receptor alpha (PPARA) and exacerbate diet-induced metabolic dysfunction. Collectively our work implicates dysregulated pre-mRNA polyadenylation in obesity-induced liver disease and uncovers a novel role for SRSF10 in this process.

2022-05-20 | PXD029228 | Pride

Identification of WTAP complex-regulated alternative splicing/polyadenylation

Project description:Identification of WTAP complex-regulated alternative splicing/polyadenylation

| PRJNA702814 | ENA

Identification of allele-specific alternative mRNA processing via transcriptome sequencing

Project description:Establishing the functional roles of genetic variants remains a significant challenge in the post-genomic era. Here, we present a method, allele-specific alternative mRNA processing (ASARP), to identify genetically influenced mRNA processing events using transcriptome sequencing (RNA-Seq) data. The method examines RNA-Seq data at both single nucleotide and whole-gene/isoform levels to identify allele-specific expression (ASE) and existence of allele-specific regulation of mRNA processing. We applied the methods to data obtained from the human glioblastoma cell line U87MG and primary breast cancer tissues and found that 26–45% of all genes with sufficient read coverage demonstrated ASE, with significant overlap between the two cell types. Our methods predicted potential mechanisms underlying ASE due to regulations affecting either whole-gene-level expression or alternative mRNA processing, including alternative splicing, alternative polyadenylation and alternative transcriptional initiation. Allele-specific alternative splicing and alternative polyadenylation may explain ASE in hundreds of genes in each cell type. Reporter studies following these predictions identified the causal single nucleotide variants (SNVs) for several allele-specific alternative splicing events. Finally, many genes identified in our study were also reported as disease/phenotype-associated genes in genome-wide association studies. Future applications of our approach may provide ample insights for a better understanding of the genetic basis of gene regulation underlying phenotypic diversity and disease mechanisms.

2012-03-30 | GSE29738 | GEO

Alternative Isoform Regulation in Human Tissue Transcriptomes

Project description:Through alternative processing of pre-mRNAs, individual mammalian genes often produce multiple mRNA and protein isoforms that may have related, distinct or even opposing functions. Here we report an in-depth analysis of 15 diverse human tissue and cell line transcriptomes based on deep sequencing of cDNA fragments, yielding a digital inventory of gene and mRNA isoform expression. Analysis of mappings of sequence reads to exon-exon junctions indicated that ~94% of human genes undergo alternative splicing (AS), ~86% with a minor isoform frequency of 15% or more. Differences in isoform-specific read densities indicated that a majority of AS and alternative cleavage and polyadenylation (APA) events exhibit variation between tissues. Variations in alternative mRNA isoform expression between 6 individuals were also detected in cerebellar cortex, with ~2- to 3-fold less isoform variation observed between individuals than between tissues. Extreme or 'switch-like' regulation of splicing between tissues was associated with increased sequence conservation and with generation of full-length open reading frames. Patterns of AS and APA were strongly correlated across tissues, suggesting coordinated regulation, and sequence conservation of known regulatory motifs in both regulated introns and 3' UTRs suggested common involvement of the same factors in regulation of tissue-specific splicing and polyadenylation. Exam mRNA expression in 15 human tissues and cell lines

2008-09-30 | E-GEOD-12946 | biostudies-arrayexpress

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