hCLE/C14orf166/RTRAF, DDX1 and HSPC117 are components of cytoplasmic mRNA-transporting granules kinesin-associated in dendrites. They have also been found in cytoplasmic ribosome-containing RNA granules that transport specific mRNAs halted for translation until specific neuronal signals renders them accessible to the translation machinery. hCLE associates to DDX1, HSPC117 and FAM98B in HEK293T cells and all four proteins bind to cap analog-containing resins. Competition and elution experiments indicate that binding of hCLE complex to cap resins is independent of eIF4E; the cap-binding factor needed for translation. Purified hCLE free of its associated proteins binds cap with low affinity suggesting that its interacting proteins modulate its cap association. hCLE silencing reduces hCLE accumulation and that of its interacting proteins and decreases mRNA translation. hCLE-associated RNAs have been isolated and sequenced; RNAs involved in mRNA translation are specifically associated. The data suggest a positive role of hCLE complex modulating mRNA translation. Overall design: Standard RNA-seq protocol was applied for comparing two sample types (HEK293T cells transfected with hCLE-TAP plasmid or empty TAP) with two biological replicates each. More than 20 million single-end, strand-specific 50 nt reads were generated for each sample.
hCLE/RTRAF-HSPC117-DDX1-FAM98B: A New Cap-Binding Complex That Activates mRNA Translation.
Cell line, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Pint lincRNA connects the p53 pathway with epigenetic silencing by the Polycomb repressive complex 2.
Specimen part, Disease, Cell line, Treatment, Subject
View SamplesIt has been recently shown that the transcription factor p53 induces the expression of multiple lincRNAs. However, relatively little is known about the role that lincRNAs play in this pathway. Here we characterize a lincRNA named PINT (p53 Induced Noncoding Transcript). We show that PINT is a ubiquitously expressed lincRNA that is finely regulated by p53. In mouse cells, PINT promotes cell proliferation and survival by regulating the expression of genes of TGF-beta, MAPK and p53 pathways. PINT is a nuclear lincRNA that directly interacts with Polycomb Repressive Complex 2 (PRC2), being required for PRC2 targeting of specific genes for repression. Furthermore, PINT functional activity is dependent on PRC2 expression, representing a connection between the p53 pathway and epigenetic regulation by PRC2. We have also identified PINT human ortholog (hPINT), which presents suggestive analogies with the mouse lincRNA. hPINT is similarly regulated by p53, and its expression correlates significantly with the same cellular pathways as the mouse ortholog, including the p53 pathway. Interestingly, hPINT is significantly downregulated in colon cancer, representing a novel tumor suppressor candidate. Our results not only help our understanding of the role of p53 and lincRNAs in cancer, but also contribute to the open debate regarding the utility of mouse models for the study of lincRNAs.
Pint lincRNA connects the p53 pathway with epigenetic silencing by the Polycomb repressive complex 2.
Specimen part, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Genome-wide analysis of the human p53 transcriptional network unveils a lncRNA tumour suppressor signature.
Cell line, Treatment
View SamplesWe report the application of high-throughput sequencing to performed the p53 regulated trancriptome in HCT116 colon cancer cells treated with the DNA damage 5FU. To study the direct targets of p53 we performed ChIP-seq to deterrmined the p53 biding sites and associated with the expression levels. With this study we identified the new genomic regions regulated by p53 and with special attention in those regions that are significally expressed by DNA damage and and are non- coding.
Genome-wide analysis of the human p53 transcriptional network unveils a lncRNA tumour suppressor signature.
Cell line, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
A Long Noncoding RNA Regulates Sister Chromatid Cohesion.
Cell line
View SamplesLong noncoding RNAs (lncRNAs) have appeared to be involved in the most diverse cellular processes through multiple mechanisms. Here we describe a previously uncharacterized human lncRNA, CONCR (cohesion regulator noncoding RNA), transcriptionally activated by MYC, which is upregulated in multiple cancer types. The expression of CONCR is cell cycle-regulated, and it is required for cell cycle progression and DNA replication. Moreover, cells depleted of CONCR show severe defects in sister chromatid cohesion, suggesting an essential role for CONCR in cohesion establishment during cell division. CONCR interacts with and regulates the activity of DDX11, a DNA-dependent ATPase and helicase involved in DNA replication. These findings suggest a novel mechanism of action for CONCR in the modulation of DDX11 enzymatic activity, unveiling the direct involvement of a lncRNA in the establishment of sister chromatid cohesion.
A Long Noncoding RNA Regulates Sister Chromatid Cohesion.
Cell line
View SamplesGene expression of periphereal blood lymphocytes (PBLs) of patients with metastatic renal cell carcinoma pre and post immunotherapy was accessed and pre therapy gene expression was compared to PBL gene expression of healthy volunteers
Gene expression profile of peripheral blood lymphocytes from renal cell carcinoma patients treated with IL-2, interferon-α and dendritic cell vaccine.
Specimen part, Disease, Disease stage
View SamplesIt is now obvious that the majority of cellular transcripts do not code for proteins, and a significant subset of them are long noncoding RNAs (lncRNAs). Many lncRNAs show aberrant expression in cancer, and some of them have been linked to cellular transformation. However, the underlying mechanisms remain poorly understood. Here we characterize the function of the p53-regulated human lncRNA LINC-PINT in cancer. We found that LINC-PINT acts as tumor suppressor lncRNA. Its expression is downregulated in multiple types of cancer and correlates with good prognosis in lung adenocarcinoma. LINC-PINT inhibits the migration capacity and invasive phenotype of cancer cells in vitro and in vivo, and it does so by repressing a proinvasion gene signature in a PRC2-dependent manner. By applying cross-species conservation analysis combined with functional experimental validations we found that the function of LINC-PINT is highly dependent on a short sequence conserved across mammals, sequence that mediates the interaction with PRC2. We propose that LINC-PINT may function as a molecular exchanger that provides PRC2 to active gene promoters for their silencing, mechanisms that could be shared by other PRC2-interacting lncRNAs.
The human lncRNA LINC-PINT inhibits tumor cell invasion through a highly conserved sequence element.
Specimen part, Cell line
View SamplesWe recently showed that the mammalian genome encodes more than a thousand large intergenic non-coding RNAs (lincRNAs) that are clearly conserved across mammals and thus functional. Gene expression patterns have implicated these lincRNAs in diverse biological processes including cell cycle regulation, immune surveillance, and embryonic stem cell pluripotency. However, the mechanism by which these lincRNAs function is unknown. Here, we expand the catalog of human lincRNAs to ~3300 by analyzing chromatin-state maps of various human cell types. Inspired by the observation that the well-characterized lincRNA HOTAIR bind the Polycomb Repressive Complex 2 (PRC2), we tested whether many lincRNAs are physically associated with PRC2. Remarkably, we observe that ~20% of lincRNAs expressed in various cell types are bound by PRC2, and that additional lincRNAs are bound by other chromatin-modifying complexes. Moreover, we show that siRNA-mediated depletion of certain lincRNAs associated with PRC2 leads to changes in gene expression and that the upregulated genes are enriched for those normally silenced by PRC2. We propose a model in which some lincRNAs guide chromatinmodifying complexes to specific genomic loci to regulate gene expression.
Many human large intergenic noncoding RNAs associate with chromatin-modifying complexes and affect gene expression.
Specimen part, Cell line
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