Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA275975 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR1812110.fastq.gz | Fastqsanger.gz | |||
| SRR1812111.fastq.gz | Fastqsanger.gz | |||
| SRR1812112.fastq.gz | Fastqsanger.gz | |||
| SRR1812113.fastq.gz | Fastqsanger.gz | |||
| SRR1812114.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 6 |
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Project description:Tristetraprolin family of proteins regulate mRNA stability by binding to specific AU-rich elements in transcripts. This binding promotes the shortening of the mRNA poly(A) tail, or deadenylation, initiating mRNA degradation. The CCR4-NOT complex plays a central role in deadenylation, while the cytoplasmic poly(A)-binding protein PABPC1 typically protects mRNAs from decay. Here, we investigate how tristetraprolin interacts with CCR4-NOT and PABPC1 to control mRNA stability. Using purified proteins and in vitro assays, we find that tristetraprolin engages CCR4-NOT through multiple interaction sites and promotes its activity, emphasizing the importance of multivalent binding for efficient deadenylation. Phosphorylation of tristetraprolin does not affect its interaction with CCR4-NOT or its deadenylation activity, but is essential for tristetraprolin binding to PABPC1. We propose that tristetraprolin promotes the processive deadenylation activity of CCR4-NOT on mRNAs containing AU-rich elements, with phosphorylation-dependent interactions with PABPC1 potentially enhancing deadenylation and promoting regulated mRNA decay.
2025-06-30 | MSV000098386 | MassIVE
Project description:The inflammatory response plays out over time in a reproducible and organized manner after an initiating stimulus. Here we showed that the genes activated in cultured mouse fibroblasts in response to the proinflammatory cytokine tumor necrosis factor can be divided roughly into three groups, each with different induction kinetics. Whereas differential transcription is important in determining the grouping of these genes, differential mRNA stability also exerted strong influence in some cases overriding that of transcriptional control elements on the temporal order of gene expression. mRNA transcripts expressed early after TNF stimulation have abundant AU-rich elements in their 3'-untranslated regions whereas those expressed later are contain fewer AU-rich sequences. Thus mRNA stability and transcriptional control, two intrinsic characteristics of genes, control the kinetics of proinflammatory cytokine-induced gene expression.
2009-01-07 | GSE14071 | GEO
Project description:The inflammatory response plays out over time in a reproducible and organized manner after an initiating stimulus. Here we showed that the genes activated in cultured mouse fibroblasts in response to the proinflammatory cytokine tumor necrosis factor can be divided roughly into three groups, each with different induction kinetics. Whereas differential transcription is important in determining the grouping of these genes, differential mRNA stability also exerted strong influence in some cases overriding that of transcriptional control elements on the temporal order of gene expression. mRNA transcripts expressed early after TNF stimulation have abundant AU-rich elements in their 3'-untranslated regions whereas those expressed later are contain fewer AU-rich sequences. Thus mRNA stability and transcriptional control, two intrinsic characteristics of genes, control the kinetics of proinflammatory cytokine-induced gene expression. Experiment Overall Design: The gene expression levels were monitored in the mouse embryonic cells stimulated with TNF for 0, 0.5h, 2h and 12 hours.
2009-01-18 | E-GEOD-14071 | biostudies-arrayexpress
Project description:Regulation of mRNA stability by RNA-protein interactions contributes significantly to quantitative aspects of gene expression. We have identified potential mRNA targets of the AU-rich element binding protein AUF1. Myc-tagged AUF1 p42 was induced in mouse NIH-3T3 cells and RNA-protein complexes isolated using anti-myc tag antibody beads. Bound mRNAs were analyzed with Affymetrix microarrays. We have identified 508 potential target mRNAs that were at least 3-fold enriched compared to control cells without myc-AUF1. 22.3% of the enriched mRNAs had an AU-rich cluster in the ARED Organism database, against 16.3% of non-enriched control mRNAs. The enrichment towards AU-rich elements was also visible by AREScore with an average value of 5.2 in the enriched mRNAs versus 4.2 in the control group. Yet, many mRNAs were enriched without a high ARE score suggesting that AUF1 has a broader binding spectrum than standard AUUUA repeats. AUF1 did not preferentially bind to unstable mRNAs. Still, some enriched mRNAs were highly unstable, as those of TNFSF11 (known as RANKL), KLF10, HES1, CCNT2, SMAD6, and BCL6. We have mapped some of the instability determinants. HES1 mRNA appeared to have a coding region determinant. Detailed analysis of the RANKL and BCL6 3’UTR revealed for both that full instability required two elements, which are conserved in evolution. In RANKL mRNA both elements are AU-rich and separated by 30 bases, while in BCL6 mRNA one is AU-rich and 60 bases from a non AU-rich element that potentially forms a stem-loop structure.
2015-09-30 | GSE64761 | GEO
Project description:The post-transcriptional control of mRNA stability plays a critical role in numerous biological functions, including the immune response, cell cycle regulation and DNA damage response. HNRNPA0, which encodes an RNA-binding protein shown to regulate transcript stability via binding to the AU-rich elements (AREs) of mRNAs, is located within the commonly deleted segment of 5q31.2 in therapy-related myeloid neoplasms (t-MNs) with a del(5q). We hypothesized that loss of HNRNPA0 leads to alterations in hematopoietic differentiation due to changes in the expression of its target AU-rich transcripts. Using RNAi interference to model Hnrnpa0 loss in primary murine cells and an experimental cell system, we found that reduced Hnrnpa0 expression leads to a shift from monocytic towards granulocytic differentiation. Microarray-based global expression profiling revealed that Hnrnpa0 knockdown disproportionally impacts ARE-containing transcripts and alters expression of myeloid specification genes. The biological importance of ARE-containing genes in myeloid neoplasms is further supported by changes in gene expression of ARE-mRNAs in t-MN del(5q) patients, predicted by pathway analysis to activate tumor growth. Together, our findings suggest that alterations in ARE-containing genes can positively regulate the cellular proliferation of del(5q) cells and implicate haploinsufficiency of HNRNPA0 as one of the key initiation mutations in the pathogenesis of t-MN. Gene expression profiling was performed on 38 single t-MN tumor samples. No control or reference samples were included.
2013-08-08 | E-GEOD-39991 | biostudies-arrayexpress
Project description:The growth factor interleukin-3 (IL-3) promotes the survival and growth of multipotent hematopoietic progenitors and stimulates myelopoiesis. It has also been reported to oppose terminal granulopoiesis and to support leukemic cell growth through autocrine or paracrine mechanisms. We used kinetic microarray, Northern Blotting and bioinformatics analysis of IL-3 dependent myeloblasts to determine whether IL-3 acts in part by regulating the rate of turnover of mRNA transcripts in specific functional pathways. Our results indicate that exposure of myeloblasts to IL-3 causes immediate early stabilization of hundreds of transcripts in pathways relevant to myeloblast function. Examples include transcripts associated with proliferation and leukemic transformation (pik3cd, myb, pim-1), hematopoietic development (cited2), differentiation control (cdkn1a) and RNA processing (BRF1, BRF2). A domain in the 3’-utr of IL-6 that mediates IL-3 responsiveness contains AU-rich elements that bind proteins known to modulate mRNA stability, however a known destabilizing protein (AUF1) is shown not to mediate degradation in the absence of IL-3. These findings support a model of IL-3 action through mRNA stability control and suggest that aberrant stabilization of this network of transcripts could contribute to growth patterns observed in leukemia.
2009-06-01 | GSE12067 | GEO
Project description:The stability of mRNAs is regulated by signals within their sequences, but a systematic and predictive understanding of the underlying sequence rules remains elusive. Here, we introduce UTR-Seq, a combination of massively parallel reporter assays and regression models, to survey the dynamics of tens-of-thousands of 3’UTR sequences during early zebrafish embryogenesis. UTR-Seq revealed two temporal degradation programs: a maternally encoded early-onset program and a late-onset program that accelerated degradation after zygotic genome activation. Three signals regulated early-onset rates: stabilizing poly-U and UUAG sequences, and destabilizing GC-rich signals. Three signals explained late-onset degradation: miR-430 seeds, AU-rich sequences and Pumilio recognition sites. Sequence based regression models translated 3’UTRs into their unique decay patterns, and predicted the in vivo impact of sequence signals on mRNA stability. Their application led to the successful design of artificial 3’UTRs that conferred specific mRNA dynamics. UTR-Seq provides a general strategy to uncover the rules of RNA cis-regulation.
2017-12-12 | GSE106677 | GEO
Project description:Tristetraprolin (TTP) binds to specific AU-rich elements in the 3'UTR of certain transcripts and regulates post-transcriptional gene expression by increasing the rate of mRNA turnover. Here, we generated a novel TTP mouse line (TTPΔARE) with a 136 base deletion in the 3'UTR AU-rich region of TTP mRNA, which resulted in a moderate increase in TTP protein expression in many tissues. In this study, we evaluated the effects of the moderate TTP overexpression on the overall pattern of gene expression in spleen, to investigate the effect of this mutation on mRNA targets of TTP under normal conditions. We utilized "TTPΔARE" (136 b deletion in the 3'UTR AU-rich region of Zfp36 mRNA) mice that overexpress TTP and compared the transcriptomic changes to the littermate "WT" mice. Spleen mRNA from four WT and four "TTPΔARE" mice were subjected to mRNA-Seq. All the animals used in this study were males between the ages of 8-12 weeks and were on a C57BL/6 background.
2019-01-19 | GSE65357 | GEO
Project description:The post-transcriptional control of mRNA stability plays a critical role in numerous biological functions, including the immune response, cell cycle regulation and DNA damage response. HNRNPA0, which encodes an RNA-binding protein shown to regulate transcript stability via binding to the AU-rich elements (AREs) of mRNAs, is located within the commonly deleted segment of 5q31.2 in therapy-related myeloid neoplasms (t-MNs) with a del(5q). We hypothesized that loss of HNRNPA0 leads to alterations in hematopoietic differentiation due to changes in the expression of its target AU-rich transcripts. Using RNAi interference to model Hnrnpa0 loss in primary murine cells and an experimental cell system, we found that reduced Hnrnpa0 expression leads to a shift from monocytic towards granulocytic differentiation. Microarray-based global expression profiling revealed that Hnrnpa0 knockdown disproportionally impacts ARE-containing transcripts and alters expression of myeloid specification genes. The biological importance of ARE-containing genes in myeloid neoplasms is further supported by changes in gene expression of ARE-mRNAs in t-MN del(5q) patients, predicted by pathway analysis to activate tumor growth. Together, our findings suggest that alterations in ARE-containing genes can positively regulate the cellular proliferation of del(5q) cells and implicate haploinsufficiency of HNRNPA0 as one of the key initiation mutations in the pathogenesis of t-MN.
2013-08-08 | GSE39991 | GEO
Project description:The growth factor interleukin-3 (IL-3) promotes the survival and growth of multipotent hematopoietic progenitors and stimulates myelopoiesis. It has also been reported to oppose terminal granulopoiesis and to support leukemic cell growth through autocrine or paracrine mechanisms. We used kinetic microarray, Northern Blotting and bioinformatics analysis of IL-3 dependent myeloblasts to determine whether IL-3 acts in part by regulating the rate of turnover of mRNA transcripts in specific functional pathways. Our results indicate that exposure of myeloblasts to IL-3 causes immediate early stabilization of hundreds of transcripts in pathways relevant to myeloblast function. Examples include transcripts associated with proliferation and leukemic transformation (pik3cd, myb, pim-1), hematopoietic development (cited2), differentiation control (cdkn1a) and RNA processing (BRF1, BRF2). A domain in the 3’-utr of IL-6 that mediates IL-3 responsiveness contains AU-rich elements that bind proteins known to modulate mRNA stability, however a known destabilizing protein (AUF1) is shown not to mediate degradation in the absence of IL-3. These findings support a model of IL-3 action through mRNA stability control and suggest that aberrant stabilization of this network of transcripts could contribute to growth patterns observed in leukemia. Cells were exposed to actinomycin D to block transcription for 0, 2 or 4 hours. The cytokine IL-3 was added after actinomycin D either at a high (1 ng/ml) or low (10 pg/ml) concentration. The effect of cytokine on transcript decay rates was therefore determined. There were five determinations per experiment (0 hour, and 2 hr and 4 hours, the latter two time points at both high and at low IL3); two independent experiments are represented (10 microarray analyses in total).
2009-06-01 | E-GEOD-12067 | biostudies-arrayexpress