A dynamic network reveals the novel characteristics of miRNA regulation over time in response to the ABA hormone in Arabidopsis (microRNA)
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ABSTRACT:
ORGANISM(S): Arabidopsis thaliana
PROVIDER: GSE145208 | GEO | 2021/04/01
REPOSITORIES: GEO
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Project description:MicroRNAs (miRNAs) participate in post-transcriptional regulation as short non-coding RNAs together with the transcription factors (TFs) and other regulatory factors such as alternative splicing (AS), which constitute complex gene regulatory networks. Following stimulation with ABA in Arabidopsis, we performed RNA-seq and small RNA-seq simultaneously at consecutive time points, and found that miRNAs respond rapidly under stress condition. Further functional analyses revealed that miRNAs classified according to different response time points play a role by binding different target genes. Systematic analysis including the static network of TF-target, TF-miRNA, miRNA-target and the time series DEGs and DE-miRNAs revealed a miRNA-mRNA dynamic regulatory network. We found that miRNAs in miRNA-containing feed-forward loops (M-FFLs) could enhance co-expression and crosstalks between different FFLs of network. Additionally, the differential transcript usage (DTU) and differential alternative splicing (DAS) analysis increased regulatory diversity between miRNA and its target genes. Collectively, our findings highlighted the systematical and precise post-transcriptional regulation of miRNAs in plant.
2021-04-01 | GSE145207 | GEO
Project description:Post-transcriptional regulation of gene expression accomplished by microRNAs (miRNAs) importantly affects the complex gene regulatory network. In particular, miRNAs are known to be involved in recurrent motifs named miRNA-mediated feed forward loops (FFLs) where a transcription factor (TF) regulates a miRNA and they both regulate the expression level of a target RNA. Here, we focus on the identification of active FFLs during adipogenic differentiation. A list of putative feed-forward loops was generated based on sequence analysis of conserved and overrepresented motifs in the regulatory regions. Since this approach is not specific for adipogenesis and is known to generate false positive feed-forward loops, an experiment was designed to select active ones based on their dynamics using a model-based approach. Microarray time series of gene and miRNA expression data were collected at seven time points on human multipotent adipose-derived stem (hMADS) cells upon adipogenic differentiation. Three different dynamic models, sharing the same FFL topology but incorporating descriptions of increasing complexity of miRNA and mRNA dynamics, are identified on miRNA and mRNA expression data and compared based on identification criteria, namely: goodness of fit, precision of the estimates and comparison with submodels. 24 FFLs, able to properly reproduce data, are selected as active out of the 329 putative ones. This method considerably reduces the search space for new interactions between TFs, miRNAs and mRNAs and provides interesting biological results identifying genes known from the literature to be regulators in adipogenesis and adipocyte-related functions that can be interpreted as positive control of the validity of the apporoach. Therefore, the genes in the selected FFLs that are not yet known to be involved in this context are potential novel players in this regulatory network of adipogenesis and adipocyte function. Two independent cell culture experiments were performed as biological replicates during adipogenic differentiation of human mesenchymal stem cell. Cells where harvested at the pre-confluent stage as reference (day -3) and at seven subsequent time points during human adipogenic differentiation: day -2 and 0 before, and 1, 2, 5, 10, 15 days after induction of differentiation. All hybridizations were repeated with reversed dye assignment (dye-swap).
2011-12-20 | E-GEOD-29185 | biostudies-arrayexpress
Project description:Post-transcriptional regulation of gene expression accomplished by microRNAs (miRNAs) importantly affects the complex gene regulatory network. In particular, miRNAs are known to be involved in recurrent motifs named miRNA-mediated feed forward loops (FFLs) where a transcription factor (TF) regulates a miRNA and they both regulate the expression level of a target RNA. Here, we focus on the identification of active FFLs during adipogenic differentiation. A list of putative feed-forward loops was generated based on sequence analysis of conserved and overrepresented motifs in the regulatory regions. Since this approach is not specific for adipogenesis and is known to generate false positive feed-forward loops, an experiment was designed to select active ones based on their dynamics using a model-based approach. Microarray time series of gene and miRNA expression data were collected at seven time points on human multipotent adipose-derived stem (hMADS) cells upon adipogenic differentiation. Three different dynamic models, sharing the same FFL topology but incorporating descriptions of increasing complexity of miRNA and mRNA dynamics, are identified on miRNA and mRNA expression data and compared based on identification criteria, namely: goodness of fit, precision of the estimates and comparison with submodels. 24 FFLs, able to properly reproduce data, are selected as active out of the 329 putative ones. This method considerably reduces the search space for new interactions between TFs, miRNAs and mRNAs and provides interesting biological results identifying genes known from the literature to be regulators in adipogenesis and adipocyte-related functions that can be interpreted as positive control of the validity of the apporoach. Therefore, the genes in the selected FFLs that are not yet known to be involved in this context are potential novel players in this regulatory network of adipogenesis and adipocyte function. Two independent cell culture experiments were performed as biological replicates during adipogenic differentiation of human mesenchymal stem cell. Cells where harvested at the pre-confluent stage as reference (day -3) and at seven subsequent time points during human adipogenic differentiation: day -2 and 0 before, and 1, 2, 5, 10, 15 days after induction of differentiation. All hybridizations were repeated with reversed dye assignment (dye-swap).
2011-12-20 | E-GEOD-29182 | biostudies-arrayexpress
Project description:Post-transcriptional regulation of gene expression accomplished by microRNAs (miRNAs) importantly affects the complex gene regulatory network. In particular, miRNAs are known to be involved in recurrent motifs named miRNA-mediated feed forward loops (FFLs) where a transcription factor (TF) regulates a miRNA and they both regulate the expression level of a target RNA. Here, we focus on the identification of active FFLs during adipogenic differentiation. A list of putative feed-forward loops was generated based on sequence analysis of conserved and overrepresented motifs in the regulatory regions. Since this approach is not specific for adipogenesis and is known to generate false positive feed-forward loops, an experiment was designed to select active ones based on their dynamics using a model-based approach. Microarray time series of gene and miRNA expression data were collected at seven time points on human multipotent adipose-derived stem (hMADS) cells upon adipogenic differentiation. Three different dynamic models, sharing the same FFL topology but incorporating descriptions of increasing complexity of miRNA and mRNA dynamics, are identified on miRNA and mRNA expression data and compared based on identification criteria, namely: goodness of fit, precision of the estimates and comparison with submodels. 24 FFLs, able to properly reproduce data, are selected as active out of the 329 putative ones. This method considerably reduces the search space for new interactions between TFs, miRNAs and mRNAs and provides interesting biological results identifying genes known from the literature to be regulators in adipogenesis and adipocyte-related functions that can be interpreted as positive control of the validity of the apporoach. Therefore, the genes in the selected FFLs that are not yet known to be involved in this context are potential novel players in this regulatory network of adipogenesis and adipocyte function.
2011-12-20 | GSE29185 | GEO
Project description:Post-transcriptional regulation of gene expression accomplished by microRNAs (miRNAs) importantly affects the complex gene regulatory network. In particular, miRNAs are known to be involved in recurrent motifs named miRNA-mediated feed forward loops (FFLs) where a transcription factor (TF) regulates a miRNA and they both regulate the expression level of a target RNA. Here, we focus on the identification of active FFLs during adipogenic differentiation. A list of putative feed-forward loops was generated based on sequence analysis of conserved and overrepresented motifs in the regulatory regions. Since this approach is not specific for adipogenesis and is known to generate false positive feed-forward loops, an experiment was designed to select active ones based on their dynamics using a model-based approach. Microarray time series of gene and miRNA expression data were collected at seven time points on human multipotent adipose-derived stem (hMADS) cells upon adipogenic differentiation. Three different dynamic models, sharing the same FFL topology but incorporating descriptions of increasing complexity of miRNA and mRNA dynamics, are identified on miRNA and mRNA expression data and compared based on identification criteria, namely: goodness of fit, precision of the estimates and comparison with submodels. 24 FFLs, able to properly reproduce data, are selected as active out of the 329 putative ones. This method considerably reduces the search space for new interactions between TFs, miRNAs and mRNAs and provides interesting biological results identifying genes known from the literature to be regulators in adipogenesis and adipocyte-related functions that can be interpreted as positive control of the validity of the apporoach. Therefore, the genes in the selected FFLs that are not yet known to be involved in this context are potential novel players in this regulatory network of adipogenesis and adipocyte function.
2011-12-20 | GSE29182 | GEO
Project description:Chinese cedar (<i>Cryptomeria fortunei</i>) is a tree species with important ornamental, medicinal, and economic value. Terpenoids extracted from the essential oil of <i>C. fortunei</i> needles have been considered valuable ingredients in the pharmaceutical and cosmetic industries. However, the possible gene regulation mechanisms that limit terpenoid biosynthesis in this genus are poorly understood. Here, we adopted integrated metabolome analysis, transcriptome, small-RNA (sRNA), and degradome sequencing to analyze the differences in terpenoid regulatory mechanisms in two different overwintering <i>C. fortunei</i> phenotypes (wild-type and an evergreen mutant). A total of 1447/6219 differentially synthesized metabolites (DSMs)/unigenes (DEGs) were detected through metabolome/transcriptome analyses, and these DSMs/DEGs were significantly enriched in flavonoid and diterpenoid biosynthesis pathways. In <i>C. fortunei</i> needles, 587 microRNAs (miRNAs), including 67 differentially expressed miRNAs (DERs), were detected. Among them, 8346 targets of 571 miRNAs were predicted using degradome data, and a 72-miRNA-target regulatory network involved in the metabolism of terpenoids and polyketides was constructed. Forty-one targets were further confirmed to be involved in terpenoid backbone and diterpenoid biosynthesis, and target analyses revealed that two miRNAs (i.e., aly-miR168a-5p and aof-miR396a) may be related to the different phenotypes and to differential regulation of diterpenoid biosynthesis. Overall, these results reveal that <i>C. fortunei</i> plants with the evergreen mutation maintain high terpenoid levels in winter through miRNA-target regulation, which provides a valuable resource for essential oil-related bioengineering research.
2022-08-12 | MTBLS3183 | MetaboLights
Project description:Results: MiRNA expression profiling of 1281 human miRNAs revealed relevant expression of 221 miRNAs consistently expressed in all samples at all time points. Correlation of platelet miRNA ranks was highly significant with data from other studies. Global distribution of miRNA expression was relatively similar in all subjects. No miRNA exhibited a significant effect of time at level 0.05. This finding was supported by exploratory analysis of predicted time effects from the mixed effects models. Furthermore, no significant effect of ASA could be found. Concerning the functional implication of the 20 most abundantly expressed miRNAs, we found 6 functional themes: nuclear import, cell cycle, transmembrane receptor protein serine/threonine kinase signaling pathway, regulation of kinase activity, pathways in cancer, and leukocyte differentiation. Conclusion: Our study shows that the platelet miRNA profile is remarkably stable in healthy subjects and is not affected by single-dose ASA treatment. For this reason, single-point analysis of platelet miRNA profile is reasonable when inter-individual differences are studied. The functional annotation network points toward additional extra-platelet effects of platelet miRNAs. We assessed the platelet miRNA profile blood in 5 volunteers at five time points over a time course of 10 days; 24 h prior to the last blood sampling, all subjects took 500 mg acetylsalicylic acid (ASA) once. Platelet miRNA was isolated from platelet-rich plasma which was leucocyte-depleted by negative bead separation. Then miRNA array analysis was performed on the isolated platelet miRNA. Temporal patterns and the effect of ASA were explored by a linear mixed effects model for each miRNA. For the 20 most abundantly expressed platelet miRNAs, a target gene search was performed by using miRWalk for validated and predicted targets. To visualize which molecular functions arerelated to those miRNAs, an annotation network was created by ClueGO, a Cytoscape plug-in.
2012-06-19 | E-GEOD-33215 | biostudies-arrayexpress
Project description:For androgen-independent prostate cancer (AIPC), the current treatment is limited and the prognosis is poor. We previously found miR-200b could inhibit androgen independent proliferation ability of prostate cancer cells, but the mechanism is unclear. MiRNAs plays their role by blocking translation through base-pairing with complementary mRNA and by promoting degradation of target mRNA. Unraveling the miRNA translational silencing network remains a challenge in part because a single miRNA can inhibit multiple mRNA targets and because a single mRNA can be regulated by several distinct miRNAs that act cooperatively. However, proteomics methods provide us useful tools to unravel the target genes network. This study identified the target genes of miR-200b in AIPC. It helps us to understand the mechanism of AIPC and applies several new candidate targets of AIPC treatment.
2020-08-05 | PXD006350 | Pride
Project description:Schmitz2014 - RNA triplex formation
The model is parameterized using the
parameters for gene CCDC3 from Supplementary Table S1. The two
miRNAs which form the triplex together with CCDC3 are miR-551b and
miR-138.
This model is described in the article:
Cooperative gene regulation
by microRNA pairs and their identification using a
computational workflow.
Schmitz U, Lai X, Winter F,
Wolkenhauer O, Vera J, Gupta SK.
Nucleic Acids Res. 2014 Jul; 42(12):
7539-7552
Abstract:
MicroRNAs (miRNAs) are an integral part of gene regulation
at the post-transcriptional level. Recently, it has been shown
that pairs of miRNAs can repress the translation of a target
mRNA in a cooperative manner, which leads to an enhanced
effectiveness and specificity in target repression. However, it
remains unclear which miRNA pairs can synergize and which genes
are target of cooperative miRNA regulation. In this paper, we
present a computational workflow for the prediction and
analysis of cooperating miRNAs and their mutual target genes,
which we refer to as RNA triplexes. The workflow integrates
methods of miRNA target prediction; triplex structure analysis;
molecular dynamics simulations and mathematical modeling for a
reliable prediction of functional RNA triplexes and target
repression efficiency. In a case study we analyzed the human
genome and identified several thousand targets of cooperative
gene regulation. Our results suggest that miRNA cooperativity
is a frequent mechanism for an enhanced target repression by
pairs of miRNAs facilitating distinctive and fine-tuned target
gene expression patterns. Human RNA triplexes predicted and
characterized in this study are organized in a web resource at
www.sbi.uni-rostock.de/triplexrna/.
This model is hosted on
BioModels Database
and identified by:
BIOMD0000000530.
To cite BioModels Database, please use:
BioModels Database:
An enhanced, curated and annotated resource for published
quantitative kinetic models.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to
the public domain worldwide. Please refer to
CC0
Public Domain Dedication for more information.
2013-10-23 | BIOMD0000000530 | BioModels
Project description:Results: MiRNA expression profiling of 1281 human miRNAs revealed relevant expression of 221 miRNAs consistently expressed in all samples at all time points. Correlation of platelet miRNA ranks was highly significant with data from other studies. Global distribution of miRNA expression was relatively similar in all subjects. No miRNA exhibited a significant effect of time at level 0.05. This finding was supported by exploratory analysis of predicted time effects from the mixed effects models. Furthermore, no significant effect of ASA could be found. Concerning the functional implication of the 20 most abundantly expressed miRNAs, we found 6 functional themes: nuclear import, cell cycle, transmembrane receptor protein serine/threonine kinase signaling pathway, regulation of kinase activity, pathways in cancer, and leukocyte differentiation. Conclusion: Our study shows that the platelet miRNA profile is remarkably stable in healthy subjects and is not affected by single-dose ASA treatment. For this reason, single-point analysis of platelet miRNA profile is reasonable when inter-individual differences are studied. The functional annotation network points toward additional extra-platelet effects of platelet miRNAs.
2012-06-20 | GSE33215 | GEO