Tissue-dependent regulation of miRNA activity
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA615635 | ENA |
REPOSITORIES: ENA
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Project description:miRNAs play important roles in every aspect of plant development. Small RNA regulation confers sensitivity and robustness onto gene regulatory networks, and the morphogen-like readout of small RNA mobility gradients yields sharply delineated domains of target gene expression. However, how the spatiotemporal patterns of miRNA activity are attained is less well understood. We used the high-resolution maize shoot apex transcriptome atlas (Knauer et al., 2019) together with data from small RNA-Seq, PARE analysis, small RNA in-situ hybridization, and RNAseq of weak dcl1 mutant tissues to demonstrate that miRNA accumulation and function during development is regulated in a tiissue dependent manner at the transcriptional and post-transcriptional level.
2021-03-03 | GSE147576 | GEO
Project description:Dormancy is a key feature of stem cell function in adult tissues as well as embryonic cells in the context of diapause. The establishment of dormancy is an active process that involves extensive transcriptional, epigenetic, and metabolic rewiring. How these processes are coordinated to successfully transition cells to the resting dormant state is not known. Here we show that microRNA activity, which is normally dispensable for pre-implantation development, is essential for the adaptation of early mouse embryos to the dormant state of diapause. In particular, the pluripotent epiblast depends on miRNA activity, the absence of which results in loss of pluripotency and embryo collapse. Through tissue-specific small RNA profiling of single embryos and computational analyses of miRNA targets, we identified the miRNA-protein network of diapause. Individual miRNA function contributes to combinatorial regulation by the network of most notably RNA processing and chromatin modifier proteins. Without miRNAs, multiple nuclear and cytoplasmic bodies show aberrant expression and structure in normal ESCs and fail to reorganize in response to stress. We find extensive alternative splicing in wild-type, but not miRNA-deficient ESCs, of cell cycle and metabolic regulators. Our results reveal that miRNAs are critical for the transcriptional and structural rewiring of pluripotent cells in response to stress and to establish dormancy in the pluripotent state.
2024-03-26 | PXD044550 | Pride
Project description:Endogenous transcripts control miRNA levels and activity in mammalian cells by a target-dependent miRNA degradation mechanism [miRNA-Seq]
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Project description:It is widely accepted that long-term changes in synapse structure and function are mediated by rapid activity-dependent gene transcription and new protein synthesis. A growing amount of evidence suggests that the microRNA (miRNA) pathway plays an important role in coordinating these processes. Despite recent advances in this field, there remains a critical need to identify specific activity-regulated miRNAs as well as their key messenger RNA (mRNA) targets. To address these questions, we used the larval Drosophila melanogaster neuromuscular junction (NMJ) as a model synapse in which to identify novel miRNA-mediated mechanisms that control activity-dependent synaptic growth. First, we developed a screen to identify miRNAs differentially regulated in the larval CNS following spaced synaptic stimulation. Surprisingly, we identified five miRNAs (miRs-1, -8, -289, -314, and -958) that were significantly downregulated by activity. Neuronal misexpression of three miRNAs (miRs-8, -289, and -958) suppressed activity-dependent synaptic growth suggesting that these miRNAs control the translation of biologically relevant target mRNAs. Functional annotation cluster analysis revealed that putative targets of miRs-8 and -289 are significantly enriched in clusters involved in the control of neuronal processes including axon development, pathfinding, and growth. In support of this, miR-8 regulated the expression of a wingless 3M-bM-^@M-^YUTR (wg 3M-bM-^@M-^Y untranslated region) reporter in vitro. Wg is an important presynaptic regulatory protein required for activity-dependent axon terminal growth at the fly NMJ. In conclusion, our results are consistent with a model where key activity-regulated miRNAs are required to coordinate the expression of genes involved in activity-dependent synaptogenesis. larval CNS of UAS-ChR2 x C380-Gal4 following synaptic stimulation
2013-02-01 | E-GEOD-43943 | biostudies-arrayexpress
Project description:Estrogen Receptor B (ERB) is a member of the nuclear receptor family of homeostatic regulators that is frequently lost in breast cancer (BC), where its presence correlates with a better prognosis and a less aggressive clinical outcome of the disease. Contrary to ERα, its closest homolog, ERB shows also significant estrogen-independent activities, including the ability to inhibit cell cycle progression and to regulate gene transcription in the absence of the ligand. Investigating the nature and extent of this constitutive activity of ERB in BC MCF-7 cells by miRNA-Seq, we identified 127 miRNAs differentially expressed in ERB+ vs ERB- cells in the absence of ligand, including upregulated oncosuppressor miRs, such miR-30a, and downregulated onco-miRs, like miR-21. In addition, a significant fraction of >1,600 unique proteins identified in these cells by iTRAQ (isobaric Tag for Relative and Absolute Quantitation) quantitative proteomics was either increased or decreased by ERB, revealing regulation of multiple cell pathways by ligand-free receptor. Transcriptome analysis indicates that for a large number of proteins regulated by ERB the corresponding mRNAs are unaffected, including a large number of putative targets of ERB-regulated miRNAs, indicating a central role of miRNAs in mediating BC cell proteome regulation by ERB. Expression of a mimic of miR-30a-5p, a direct target and downstream effector of ERB in BC, led to the identification of several target transcripts of this miRNA, including 11 encoding proteins whose intracellular concentration is significantly affected by unliganded receptor. These results demonstrate a significant effect of ligand-free ERB on BC cell functions via modulation of the cell proteome and suggest that miRNA regulation may represent a key event in the control of the biological and clinical phenotype of hormone-responsive BC by this nuclear receptor.
2014-10-23 | PXD000499 | Pride
Project description:Endogenous transcripts control miRNA levels and activity in mammalian cells by a target-dependent miRNA degradation mechanism
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Project description:microRNA-dependent regulation of biomechanical genes establishes tissue stiffness homeostasis
2019-02-19 | PXD011882 | Pride
Project description:It is widely accepted that long-term changes in synapse structure and function are mediated by rapid activity-dependent gene transcription and new protein synthesis. A growing amount of evidence suggests that the microRNA (miRNA) pathway plays an important role in coordinating these processes. Despite recent advances in this field, there remains a critical need to identify specific activity-regulated miRNAs as well as their key messenger RNA (mRNA) targets. To address these questions, we used the larval Drosophila melanogaster neuromuscular junction (NMJ) as a model synapse in which to identify novel miRNA-mediated mechanisms that control activity-dependent synaptic growth. First, we developed a screen to identify miRNAs differentially regulated in the larval CNS following spaced synaptic stimulation. Surprisingly, we identified five miRNAs (miRs-1, -8, -289, -314, and -958) that were significantly downregulated by activity. Neuronal misexpression of three miRNAs (miRs-8, -289, and -958) suppressed activity-dependent synaptic growth suggesting that these miRNAs control the translation of biologically relevant target mRNAs. Functional annotation cluster analysis revealed that putative targets of miRs-8 and -289 are significantly enriched in clusters involved in the control of neuronal processes including axon development, pathfinding, and growth. In support of this, miR-8 regulated the expression of a wingless 3’UTR (wg 3’ untranslated region) reporter in vitro. Wg is an important presynaptic regulatory protein required for activity-dependent axon terminal growth at the fly NMJ. In conclusion, our results are consistent with a model where key activity-regulated miRNAs are required to coordinate the expression of genes involved in activity-dependent synaptogenesis.
2013-02-01 | GSE43943 | GEO
Project description:miRNA expression in lung tissue
| PRJNA437828 | ENA
Project description:It is widely accepted that long-term changes in synapse structure and function are mediated by rapid activity-dependent gene transcription and new protein synthesis. A growing amount of evidence suggests that the microRNA (miRNA) pathway plays an important role in coordinating these processes. Despite recent advances in this field, there remains a critical need to identify specific activity-regulated miRNAs as well as their key messenger RNA (mRNA) targets. To address these questions, we used the larval Drosophila melanogaster neuromuscular junction (NMJ) as a model synapse in which to identify novel miRNA-mediated mechanisms that control activity-dependent synaptic growth. First, we developed a screen to identify miRNAs differentially regulated in the larval CNS following spaced synaptic stimulation. Surprisingly, we identified five miRNAs (miRs-1, -8, -289, -314, and -958) that were significantly downregulated by activity. Neuronal misexpression of three miRNAs (miRs-8, -289, and -958) suppressed activity-dependent synaptic growth suggesting that these miRNAs control the translation of biologically relevant target mRNAs. Functional annotation cluster analysis revealed that putative targets of miRs-8 and -289 are significantly enriched in clusters involved in the control of neuronal processes including axon development, pathfinding, and growth. In support of this, miR-8 regulated the expression of a wingless 3M-bM-^@M-^YUTR (wg 3M-bM-^@M-^Y untranslated region) reporter in vitro. Wg is an important presynaptic regulatory protein required for activity-dependent axon terminal growth at the fly NMJ. In conclusion, our results are consistent with a model where key activity-regulated miRNAs are required to coordinate the expression of genes involved in activity-dependent synaptogenesis. Three technical replicates (each in raw data) of three biological replicates of wild-type (CantonS) larvae in two treatment groups: (1) 5x spaced high K; (2) or 0x mock stimulation.
2013-02-01 | E-GEOD-43944 | biostudies-arrayexpress