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Open Access Research

Depletion of T-cell intracellular antigen proteins promotes cell proliferation

Raquel Reyes, José Alcalde and José M Izquierdo*

Author Affiliations

Centro de Biología Molecular 'Severo Ochoa', Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid, C/Nicolás Cabrera 1, Lab-107, Cantoblanco DP 28049, Madrid, Spain

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Genome Biology 2009, 10:R87  doi:10.1186/gb-2009-10-8-r87

Published: 26 August 2009

Abstract

Background

T-cell intracellular antigen-1 (TIA-1) and TIA-1 related/like protein (TIAR/TIAL1), two DNA/RNA binding proteins broadly expressed in eukaryotic cells, participate in the regulation of gene expression through RNA metabolism. Despite the biological relevance of these regulators, there are no genome-wide studies assessing global transcriptomic and phenotypic impacts after changes in the expression and/or function of these proteins.

Results

Using high-throughput gene expression profiling, we found that the TIA-1/TIAR-depleted cell phenotype is linked to a transcriptome involved in the control of inflammation, cell-cell signaling, immune-suppression, angiogenesis, metabolism and cell proliferation. Induced genes included pro-inflammatory cytokines, inflammatory chemokines, growth-stimulating factors and pro-angiogenic inducers. Repressed genes involved the RAS oncogene family member RAB40B, regulators of cytoskeleton organization and biogenesis and a mitochondrial modulator. Consistent with these observations, depletion of TIA proteins in HeLa cells results in increased cell proliferation, altered cell-cycle and anchorage-independent growth. Mechanistically, the changes associated with the steady-state target mRNA levels regulated by TIA proteins are consistent with overlapping effects on gene basal transcription rate and mRNA turnover.

Conclusions

Collectively, our findings suggest a role for TIA proteins as cellular sensors that modulate gene expression control at the transcriptional and post-transcriptional levels, coupling cell proliferation responses and metabolic homeostasis to cell survival and growth.