Genome-wide analysis of TIAR RNA ligands in mouse macrophages before and after LPS stimulation
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE77577 | GEO | 2016/02/05
SECONDARY ACCESSION(S): PRJNA310852
REPOSITORIES: GEO
Similar Datasets
Project description:TIA-1 related protein (TIAR) is a RNA-binding protein involved in several steps of gene expression such RNA splicing and translation. TIAR contains three RNA recognition motifs (RRMs) allowing its interaction with specific sequences localized in the untranslated regions (UTRs) of several mRNAs. In myeloid cells, TIAR has been shown to bind and regulate the translation and stability of various mRNAs encoding proteins important for the inflammatory response, such as TNFα, Cox-2 or IL-8 . Here, we generated two macrophage-like RAW 264.7 cell lines expressing either a tagged full-length TIAR protein or a RRM2-truncated mutant unable to bind RNA with high affinity . By a combination of RNA-IP and microarray analysis (RIP-chip), we identified mRNAs specifically bound by the full-length protein both in basal conditions and in response to LPS. Microarray hybridization was performed on TIAR-FLAG-associated mRNAs or TIARÎRRM2-FLAG-associated mRNAs in unstimulated and LPS-stimulated RAW264.7 cells. Enrichment of TIAR-FLAG-associated mRNAs and TIARÎRRM2-FLAG-associated mRNAS were normalized to total transcriptome of TIAR-FLAG and TIARÎRRM2-FLAG expressing-RAW264.7 cells respectively. After amplification and labelling, sample pairs were hybridized onto Mouse Exonic Evidence Based Oligonucleotide (MEEBO) arrays containing on average 38784 mouse 70mer oligonucleotide probes (Stanford University, US). Hybridizations were replicated with dye swap.
2016-02-05 | E-GEOD-77577 | biostudies-arrayexpress
Project description:Hepatocellular carcinoma, the most common type of liver malignancy, is one of the most lethal forms of cancer. We identified a long non-coding RNA, Gm19705, that is over-expressed in hepatocellular carcinoma and mouse embryonic stem cells. We named this RNA Pluripotency and Hepatocyte Associated RNA Overexpressed in HCC, or PHAROH. Depletion of PHAROH impacts cell proliferation and migration, which can be rescued by ectopic expression of PHAROH. RNA-seq analysis of PHAROH knockouts revealed that a large number of genes with decreased expression contain a c-Myc motif in their promoter. C-MYC is decreased at the protein level, but not the mRNA level. RNA-antisense pulldown identified nucleolysin TIAR, a translational repressor, to bind to a 71-nt hairpin within PHAROH, sequestration of which increases c-MYC translation. In summary, our data suggest that PHAROH regulates c-MYC translation by sequestering TIAR and as such represents a potentially exciting diagnostic or therapeutic target in hepatocellular carcinoma.
2021-05-09 | GSE167316 | GEO
Project description:Chronic myeloid leukemia (CML) cells circulate between blood and bone marrow niche, representing different microenvironments. We studied the role of the two RNA binding proteins, T-cell-restricted intracellular antigen (TIAR) and the fragile X mental retardation protein (FMRP) in the regulation of protein translation in CML cells residing in settings mimicking peripheral blood microenvironment (PBM) and bone marrow microenvironment (BMM). We studied how conditions shaped the translation process through TIAR and FMRP activity, considering its relevance in therapy resistance. The QuaNCAT mass-spectrometric approach revealed that TIAR and FMRP have a discrete modulatory effect on protein synthesis and thus affect distinct aspects of leukemic cells functioning in the hypoxic niche. We demonstrate that TIAR substantially supports the resistance of CML cells to translation inhibition by homoharringtonine in the BMM. Overall, our results show that targeting post-transcriptional control should be considered when designing anti-leukemia therapeutic solutions.
2023-05-10 | PXD032332 | Pride
Project description:The knock down of T-cell intracellular antigen (TIA) proteins enhances the acquisition of aberrant cellular phenotypes promoting uncontrolled cell and tumor growth. Hereby, we report that inducible expression of either TIA1 or TIAR in human embryonic kidney (HEK293) cells represses cell proliferation. Mechanistically, the sustained expression of either TIA1 or TIAR protein abolishes endogenous TIA1/TIAR protein expression via regulating splicing of their own pre-mRNAs. This event is concomitant with cell cycle arrest and cell death by apoptosis. Based on genome-wide analysis of the transcript expression patterns in HuR-, TIA1- or TIAR-expressing HEK293 cells, we found regulatory links among the up-regulation on a select subset of p53 pathway genes involved in G1/S cell-cycle and apoptosis control. Finally, nude mice injected with TIA1- or TIAR-expressing HEK293 cells decrease, and even abolishing, the growth of tumor xenografts relative to control cells. Collectively, these observations show that TIA proteins can function as tumor suppressor genes.
2015-03-05 | GSE51500 | GEO
Project description:RNA was isolated from material that had been subjected to immunoprecipitation (IP) from RKO cells that were either left untreated or irradiated with 20 J/m2 UVC and collected 1h later; IP assays were carried out using either an antibody recognizing RNA-binding protein TIAR, or using a control IgG1 antibody. RNA was reverse-transcribed in the presence of [alpha-33P]dCTP and the radiolabeled product used to hybridize human cDNA arrays. The experiment was repeated using three independent sample sets. The samples were numbered Tc-1, Tc-2, Tc-3, Tuv-1, Tuv-2, Tuv-3, IgG1c-1, IgG1c-2, IgG1c-3, IgG1uv-1, IgG1uv-2, and IgG1uv-3. ‘Tc’ denotes RNA from IP reactions using untreated cells and anti-TIAR antibody, ‘Tuv’ denotes RNA from IP reactions using UVC-treated cells and anti-TIAR antibody, ‘IgG1c’ denotes RNA from IP reactions using untreated cells and anti-IgG1 antibody, and ‘IgG1uv’ denotes RNA from IP reactions using UVC-treated cells and anti-IgG1 antibody. The numbers 1, 2 and 3 correspond to the three independent experimental datasets. Keywords = post-transcriptional / translation / nascent protein synthesis / stress response / ribonomics Keywords: ordered
2004-05-27 | GSE1433 | GEO
Project description:RNA was isolated from material that had been subjected to immunoprecipitation (IP) from RKO cells that were either left untreated or irradiated with 20 J/m2 UVC and collected 1h later; IP assays were carried out using either an antibody recognizing RNA-binding protein TIAR, or using a control IgG1 antibody. RNA was reverse-transcribed in the presence of [alpha-33P]dCTP and the radiolabeled product used to hybridize human cDNA arrays. The experiment was repeated using three independent sample sets. The samples were numbered Tc-1, Tc-2, Tc-3, Tuv-1, Tuv-2, Tuv-3, IgG1c-1, IgG1c-2, IgG1c-3, IgG1uv-1, IgG1uv-2, and IgG1uv-3. âTcâ denotes RNA from IP reactions using untreated cells and anti-TIAR antibody, âTuvâ denotes RNA from IP reactions using UVC-treated cells and anti-TIAR antibody, âIgG1câ denotes RNA from IP reactions using untreated cells and anti-IgG1 antibody, and âIgG1uvâ denotes RNA from IP reactions using UVC-treated cells and anti-IgG1 antibody. The numbers 1, 2 and 3 correspond to the three independent experimental datasets. Keywords = post-transcriptional / translation / nascent protein synthesis / stress response / ribonomics Keywords: ordered
2010-06-09 | E-GEOD-1433 | biostudies-arrayexpress
Project description:Long non-coding RNAs (lncRNAs) are best known for playing diverse roles at transcriptional level. Here we report a lncRNA MT1JP for its posttranscriptional function as a modulator of tumorigenesis. By associating with RNA-binding protein TIAR, MT1JP favored the translation of vital transcription factor p53, and then regulated a series of p53 involved pathways such as cell cycle, apoptosis, proliferation and so forth. With down-regulation of MT1JP, the protein level of p53 was declined, which in turn accelerated cell deteriorate and tumor formation. Moreover, differential expression of MT1JP in tumor tissues and matched normal tissues suggests that it may be an excellent prognosis and therapy target as a tumor suppressor. Together, our finding identifies MT1JP as a critical lncRNA required for restraining tumorigenesis, which occurs through MT1JP interacting with TIAR to modulate p53 translation.
2018-06-15 | GSE69870 | GEO
Project description:The knock down of T-cell intracellular antigen (TIA) proteins enhances the acquisition of aberrant cellular phenotypes promoting uncontrolled cell and tumor growth. Hereby, we report that inducible expression of either TIA1 or TIAR in human embryonic kidney (HEK293) cells represses cell proliferation. Mechanistically, the sustained expression of either TIA1 or TIAR protein abolishes endogenous TIA1/TIAR protein expression via regulating splicing of their own pre-mRNAs. This event is concomitant with cell cycle arrest and cell death by apoptosis. Based on genome-wide analysis of the transcript expression patterns in HuR-, TIA1- or TIAR-expressing HEK293 cells, we found regulatory links among the up-regulation on a select subset of p53 pathway genes involved in G1/S cell-cycle and apoptosis control. Finally, nude mice injected with TIA1- or TIAR-expressing HEK293 cells decrease, and even abolishing, the growth of tumor xenografts relative to control cells. Collectively, these observations show that TIA proteins can function as tumor suppressor genes. Two independent biological replicates were performed per sample type. Agilent SurePrint G3 Human Gene Expression 8x60K v2 array were used in all cases (single-channel hybridizations)
2015-03-05 | E-GEOD-51500 | biostudies-arrayexpress
Project description:Background: Mice lacking either T-cell intracellular antigen 1 (TIA1) or TIA1-related/like protein (TIAR/TIAL1) show high rates of embryonic lethality, suggesting a relevant role for these proteins during embryonic development. However, intrinsic molecular and cellular consequences of either TIA1 or TIAR deficiency remain poorly defined. Results: By using genome-wide expression profiling approach, we demonstrate that either TIA1 or TIAR inactivation broadly alter normal development-associated signaling pathways in murine embryonic fibroblasts (MEF). Indeed, these analyses highlighted alterations of cytokine-cytokine and ECM-receptor interactions and Wnt, MAPK, TGF-beta dependent signaling pathways. Consistent with these results, TIA1 and TIAR knockout (KO) MEF show reduced rates of cell proliferation, cell cycle progression delay and increased cell size. Furthermore, TIA-proteins deficiency also caused metabolic deficiencies, increased ROS levels and DNA damage, promoting a gentle rise of cell death. Concomitantly, high rates of autophagy were detected in both TIA1 and TIAR KO MEF with induction of the formation of autophagosomes, as evidenced by the up-regulation of the LC3B protein, and autolysosomes, measured by colocalization of LC3B and LAMP1, as a survival mechanism attempt. Conclusions: Taken together, these observations support that TIA proteins orchestrate a transcriptome programme to activate specific developmental decisions. This program is likely to contribute to mouse physiology starting at early stages of the embryonic development. TIA1/TIAR might function as cell sensors to maintain homeostasis and promote adaptation/survival responses to developmental stress.
2014-11-05 | GSE43077 | GEO
Project description:Background: Mice lacking either T-cell intracellular antigen 1 (TIA1) or TIA1-related/like protein (TIAR/TIAL1) show high rates of embryonic lethality, suggesting a relevant role for these proteins during embryonic development. However, intrinsic molecular and cellular consequences of either TIA1 or TIAR deficiency remain poorly defined. Results: By using genome-wide expression profiling approach, we demonstrate that either TIA1 or TIAR inactivation broadly alter normal development-associated signaling pathways in murine embryonic fibroblasts (MEF). Indeed, these analyses highlighted alterations of cytokine-cytokine and ECM-receptor interactions and Wnt, MAPK, TGF-beta dependent signaling pathways. Consistent with these results, TIA1 and TIAR knockout (KO) MEF show reduced rates of cell proliferation, cell cycle progression delay and increased cell size. Furthermore, TIA-proteins deficiency also caused metabolic deficiencies, increased ROS levels and DNA damage, promoting a gentle rise of cell death. Concomitantly, high rates of autophagy were detected in both TIA1 and TIAR KO MEF with induction of the formation of autophagosomes, as evidenced by the up-regulation of the LC3B protein, and autolysosomes, measured by colocalization of LC3B and LAMP1, as a survival mechanism attempt. Conclusions: Taken together, these observations support that TIA proteins orchestrate a transcriptome programme to activate specific developmental decisions. This program is likely to contribute to mouse physiology starting at early stages of the embryonic development. TIA1/TIAR might function as cell sensors to maintain homeostasis and promote adaptation/survival responses to developmental stress. Two independent replicates were performed for each experimental condition and hybridized to Agilent SurePrint G3 Mouse 8x60 microarrays.
2014-11-05 | E-GEOD-43077 | biostudies-arrayexpress