Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

TIA proteins drives global and specific translational repression of genes linked to the cell-cycle progression and DNA replication/repair

ABSTRACT: The reduction of T-cell intracellular antigen (TIA) proteins in transformed cells leads to the acquisition of aberrant cellular phenotypes promoting uncontrolled cell proliferation and tumor growth. Here we show that global and specific translational rates are regulatory gene events that contribute markedly to the acquisition of above cellular phenotypes. For example, we observe a significant increase of ribosomal population and translational machinery components in TIA-reduced HeLa cells. Polysomal microarray analysis shows specific changes at both the transcript and translational level following TIA reduction, identifying translationally regulated mRNAs that are not transcriptionally regulated which seem to be prevalent for the adaptation to the new environmental conditions. Validation of microarray data using RT-QPCR and immunological analysis for representative genes were carried out. Up-regulated in this class of mRNA are those involved in cell-cycle progression and DNA replication/repair, including several mRNAs with specific sequences to bind TIA proteins. Our data support a hypothesis that a concerted activation of both global and selective translational rates is relevant for the transition from quiescent to proliferative status in TIA-depleted HeLa cells. Two independent replicates were performed for each experimental condition and hybridized to SurePrint G3 Human GE 8x60K Agilent microarrays.

ORGANISM(S): Homo sapiens

SUBMITTER: Juan Oliveros

PROVIDER: E-GEOD-54540 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Genome-wide profiling reveals a role for T-cell intracellular antigens TIA1 and TIAR in the control of translational specificity in HeLa cells.

Carrascoso Isabel I Sánchez-Jiménez Carmen C Izquierdo José M JM

The Biochemical journal 20140701 1

TIA (T-cell intracellular antigens)-knockdown HeLa cells show an increase in ribosomes and translational machinery components. This increase correlates with specific changes in translationally up-regulated mRNAs involved in cell-cycle progression and DNA repair, as shown in polysomal profiling analysis. Our data support the hypothesis that a concerted activation of both global and selective translational rates leads to the transition to a more proliferative status in TIA-knockdown HeLa cells. ...[more]

PMID: 24927121

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Project description:Background: Our recent studies strongly suggest that remodeling in the control of gene expression contributes to the progression of cell phenotypes associated to the transient and permanent knock-down of T-cell intracellular antigen 1(TIA1) and TIA1 related/like (TIAR/TIAL1) proteins. In particular, our studies have been focused on transcriptomic profiling of TIA-depleted HeLa cells using transient RNA interference (siRNA-mediated) and genome-wide microarray approaches Results: This study provides, for the first time, TIA1 and TIAR linked-transcriptomic analysis by using RNA-Seq next generation sequencing technology. Illumina RNA-Seq was used to survey transcriptome profiles from permanent TIA1 and TIAR-(shRNA-mediated) deficient HeLa cells. Analysis of the transcriptomes with the Cufflinks tool revealed that differentially expressed genes, isoforms produced by alternative splicing and/or promoter usage as well as microRNAs generated a great transcriptomic heterogeneity which might reflect the complexity linked to these cell phenoypes. The data of differential expression were validated by using genome-wide microarrays and QPCR. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes term enrichment analysis revealed over-representation of genes associated with cell differentiation, multicellular organismal development, signal transduction, axon guidance and cell adhesion and under-representation of genes associated with positive regulation of migration, cell adhesion, response to organic substance, prostaglandin metabolic process and blood coagulation. Conclusions: Taken together, our observations point out towards an inhibitory role of TIA proteins in cell proliferation and growth, there appears to be an apparent molecular discrepancy regarding the effects of TIA proteins based on whether the proteins are depleted transiently (siRNA-mediated) or permanently (shRNA-mediated), suggesting the existence of clonal selection mechanisms of cellular populations in permanently TIA1/TIAR-depleted HeLa cells. For each cell type, three biological replicates were prepared and hybridized to Affymetrix GeneChips (HG U133plus2). 3+3 hybridizations in total for a single comparison KO vs WT.

Dataset Information

TIA proteins drives global and specific translational repression of genes linked to the cell-cycle progression and DNA replication/repair

Publications

Genome-wide profiling reveals a role for T-cell intracellular antigens TIA1 and TIAR in the control of translational specificity in HeLa cells.

Similar Datasets

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