Depletion of T-cell intracellular antigen proteins promotes cell proliferation.
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.
Reyes
Raquel
R
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. rreyes@cbm.uam.es
Alcalde
José
J
Izquierdo
José M
JM
D049109:Cell Proliferation; D018925:Chemokines / Q000235:genetics; D016207:Cytokines / Q000235:genetics; D020869:Gene Expression Profiling; D006367:HeLa Cells; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D039102:Poly(A)-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D000074019:T-Cell Intracellular Antigen-1
D018925:Chemokines; D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins; D039102:Poly(A)-Binding Proteins; D016601:RNA-Binding Proteins; D000074019:T-Cell Intracellular Antigen-1; C071558:TIA1 protein, human; C076751:TIAL1 protein, human