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SRP077288
Homo sapiens
24 Downloadable Samples
Illumina HiSeq 2000, NextSeq 500
Description
FAM46C is one of the most frequently mutated genes in multiple myeloma (MM) and encodes a protein of unknown function. Using a combination of in vitro and in vivo approaches, we demonstrate that FAM46C encodes an active cytoplasmic non-canonical poly(A) polymerase, which enhances mRNA stability and gene expression. Moreover, we also found that the reintroduction of active FAM46C into MM cell lines, but not its catalytically-inactive mutant, leads to broad polyadenylation and stabilization of mRNAs strongly enriched with those encoding endoplasmic reticulum-targeted proteins and induced cell death. This is, to our knowledge, the first report that directly associates cytoplasmic poly(A) polymerase with carcinogenesis. Furthermore, our data suggest that the human genome encodes at least eleven non-canonical poly(A) polymerases with four FAM46 family members. Since FAM46 proteins are differentially expressed during development, these proteins may positively regulate transcript stability and translational rate in a tissue-specific manner. Overall design: The H929 and SKMM1 MM cells were transduced with lentiviruses carrying FAM46CWTGFP (WT) or FAM46CD90A,D92AGFP (catalitic mutant). 72h after transgene delivery total RNA was extracted and RNA-seq libraries were prepared.
Publication Title
The non-canonical poly(A) polymerase FAM46C acts as an onco-suppressor in multiple myeloma.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
A doxycycline-inducible system was used to induce PU.1 expression in cultured myeloid cell lines. The parent cell line used was BN (Kamath et al., Leukemia 22:1214-1225, 2008).
Publication Title
PU.1 promotes cell cycle exit in the murine myeloid lineage associated with downregulation of E2F1.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 7 Downloadable Samples
- IlluminaHiSeq2500
Description
Human transcripts can typically be processed at multiple polyadenylation sites to yield mRNA isoforms with distinct 3 ends. A multitude of factors contributes to the choice of individual polyadenylation sites in different cell types and tissues. In this study we have found that the heterogenous ribonucleoprotein C (hnRNP C), an RNA binding protein that was previously linked to splicing and polyadenylation at Alu repeat elements, is a general regulator of pre-mRNA cleavage and polyadenylation. By sequencing mRNA 3 ends from cells expressing normal and reduced levels of hnRNP C we found that transcripts that contain poly(U) tracts around their poly(A) sites respond in a manner indicative of hnRNP C repressing cleavage and polyadenylation. The 3 UTR isoforms whose abundance is modulated by hnRNP C contain U-rich elements and can thereby interact with A/U-rich element binding proteins that have been shown to alter transcript stability, sub-cellular localization and even the localization of the translated proteins.
Publication Title
A comprehensive analysis of 3' end sequencing data sets reveals novel polyadenylation signals and the repressive role of heterogeneous ribonucleoprotein C on cleavage and polyadenylation.
Sample Metadata Fields
No sample metadata fields
View Samples- Escherichia coli
- 3 Downloadable Samples
- Affymetrix E. coli Genome 2.0 Array (ecoli2)
Description
Transcriptional analysis of the effects of the deletion of the sRNAs glmY and glmZ in EHEC
Publication Title
Global analysis of posttranscriptional regulation by GlmY and GlmZ in enterohemorrhagic Escherichia coli O157:H7.
Sample Metadata Fields
No sample metadata fields
View Samples- Caenorhabditis elegans
- 14 Downloadable Samples
- Illumina HiSeq 2500
Description
Purpose: We observed protein homeostasis modulations when anc-1 is knocked-down. We wanted to measure changes in gene expression profiles following this manipulation. Methods: We treated wild type (strain N2) or polyQ35-YFP (strain AM140) nematodes, which express toxic aggregative proteins that challenge their protein homeostasis, with anc-1 RNAi until day six of adulthood, and compared their gene expression levels to those of untreated worms. Results: The knockdown of anc-1 leads to modified expression levels of hundreds of genes. There is an enrichment of transcription factors and protein homeostasis modulators, such as E3 ubiquitin ligases. Conclusions: anc-1 regulates protection from toxic aggregative proteins, at least partially, by regulating the expression of genes that encode protein homeostasis factors. Overall design: Wild type strain, three repeats; polyQ35-YFP strain, four repeats. Each repeat has two conditions: untreated (EV), and RNAi toward anc-1.
Publication Title
Gene expression modulation by the linker of nucleoskeleton and cytoskeleton complex contributes to proteostasis.
Sample Metadata Fields
Cell line, Subject
View Samples- Rattus norvegicus
- 12 Downloadable Samples
- Affymetrix Rat Gene 1.0 ST Array (ragene10st)
Description
The present study was designed to test the hypothesis that limited growth of the fetal liver in the model of maternal fasting is independent of well-characterized signaling mechanisms that are known to regulate somatic growth in adult animals.
Publication Title
Regulation of fetal liver growth in a model of diet restriction in the pregnant rat.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Arabidopsis thaliana
- 12 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Transcriptional variation, also called expression level polymorphism (ELP), contributes to intra-specific phenotypic variation in many organisms. Differentially expressed transcripts are typically enriched for stress-related genes, suggesting that differences in response to the environment are a particularly common point of divergence among gentoypes. Analysis of ELPs also has been suggested as a way to assess unintended consequences of transgene introduction; however, it is important that interpretation of transcriptional changes be performed within the context of potential fitness effects. In these studies we sought to examine differential gene expression in response to salinity for two widely used Arabidopsis thaliana ecotypes, Wassilewskija (Ws) and Columbia (Col), and a single gene mutation (glabrous, gl1-1) in the Col background (Col(gl)), in relation to genetic, phenotypic, and fitness differences.
Publication Title
Global gene expression analysis of transgenic, mannitol-producing, and salt-tolerant Arabidopsis thaliana indicates widespread changes in abiotic and biotic stress-related genes.
Sample Metadata Fields
Age, Specimen part
View Samples- Arabidopsis thaliana
- 8 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Mannitol is a putative osmoprotectant contributing to salt tolerance in several species. Arabidopsis plants transformed with the mannose-6-phosphate reductase (M6PR) gene from celery were dramatically more salt tolerant (at 100mM NaCl) as exhibited by reduced salt injury, less inhibition of vegetative growth, and increased seed production relative to the wild type (WT). When treated with 200mM NaCl, transformants produced no seeds, but did bolt, and exhibited less chlorosis/necrosis and greater survival and dry weights than the WT. Without salt there were no M6PR effects on growth or phenotype, but expression levels of 2272 genes were altered. Many fewer differences (1039) were observed between M6PR and WT plants in the presence of salt, suggesting that M6PR pre-conditioned the plants to stress. Previous work suggested that mannitol is an osmoprotectant, but mannitol levels are invariably quite low, perhaps inadequate for osmoprotectant effects. In this study, transcriptome analysis reveals that the M6PR transgene activated the downstream abscisic acid (ABA) pathway by up-regulation of ABA receptor genes (PYL4, PYL5, and PYL6) and down-regulation of protein phosphatase 2C genes (ABI1 and ABI2). In the M6PR transgenic lines there were also increases in transcripts related to redox and cell wall-strengthening pathways. These data indicate that mannitol-enhanced stress tolerance is due at least in part to increased expression of a variety of stress-inducible genes.
Publication Title
Global gene expression analysis of transgenic, mannitol-producing, and salt-tolerant Arabidopsis thaliana indicates widespread changes in abiotic and biotic stress-related genes.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 3 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The adult pancreas is capable of limited regeneration after injury, but has no defined stem cell population. The cell types and molecular signals that govern the production of new pancreatic tissue are not well understood. Here we show that inactivation of the SCF-type E3 ubiquitin ligase substrate recognition component Fbw7 induces pancreatic ductal cells to reprogram into -cells. The induced -cells resemble islet -cells in morphology and histology, express genes essential for -cell function, and release insulin upon glucose challenge. Thus, loss of Fbw7 appears to reawaken an endocrine developmental differentiation program in adult pancreatic ductal cells. Our study highlights the plasticity of seemingly differentiated adult cells, identifies Fbw7 as a master regulator of cell fate decisions in the pancreas, and reveals adult pancreatic duct cells as a latent multipotent cell type.
Publication Title
Loss of Fbw7 reprograms adult pancreatic ductal cells into α, δ, and β cells.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Rattus norvegicus
- 40 Downloadable Samples
- Affymetrix Rat Gene 1.0 ST Array (ragene10st)
Description
Our strategy was to manipulate mTOR signaling in vivo, then characterize the transcriptome and translating mRNA in liver tissue. In adult rats, we used the non-proliferative growth model of refeeding after a period of fasting, and the proliferative model of liver regeneration following partial hepatectomy. We also studied livers from pre-term fetal rats (embryonic day 19-20) in which fetal hepatocytes are asynchronously proliferating. All three models employed rapamycin to inhibit mTOR signaling.
Publication Title
Profiling of the fetal and adult rat liver transcriptome and translatome reveals discordant regulation by the mechanistic target of rapamycin (mTOR).
Sample Metadata Fields
Specimen part, Time
View Samples