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Tissue and process specific microRNA-mRNA co-expression in mammalian development and malignancy.

ABSTRACT: An association between enrichment and depletion of microRNA (miRNA) binding sites, 3' UTR length, and mRNA expression has been demonstrated in various developing tissues and tissues from different mature organs; but functional, context-dependent miRNA regulations have yet to be elucidated. Towards that goal, we examined miRNA-mRNA interactions by measuring miRNA and mRNA in the same tissue during development and also in malignant conditions. We identified significant miRNA-mediated biological process categories in developing mouse cerebellum and lung using non-targeted mRNA expression as the negative control. Although miRNAs in general suppress target mRNA messages, many predicted miRNA targets demonstrate a significantly higher level of co-expression than non-target genes in developing cerebellum. This phenomenon is tissue specific since it is not observed in developing lungs. Comparison of mouse cerebellar development and medulloblastoma demonstrates a shared miRNA-mRNA co-expression program for brain-specific neurologic processes such as synaptic transmission and exocytosis, in which miRNA target expression increases with the accumulation of multiple miRNAs in developing cerebellum and decreases with the loss of these miRNAs in brain tumors. These findings demonstrate the context-dependence of miRNA-mRNA co-expression.

SUBMITTER: Liu H

PROVIDER: S-EPMC2673043 | biostudies-literature | 2009

REPOSITORIES: biostudies-literature

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Tissue and process specific microRNA-mRNA co-expression in mammalian development and malignancy.

Liu Hongye H Kohane Isaac S IS

PloS one 20090505 5

An association between enrichment and depletion of microRNA (miRNA) binding sites, 3' UTR length, and mRNA expression has been demonstrated in various developing tissues and tissues from different mature organs; but functional, context-dependent miRNA regulations have yet to be elucidated. Towards that goal, we examined miRNA-mRNA interactions by measuring miRNA and mRNA in the same tissue during development and also in malignant conditions. We identified significant miRNA-mediated biological pr ...[more]

PMID: 19415117

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Project description:BackgroundBerries of grape (Vitis vinifera) contain three major tissue types (skin, pulp and seed) all of which contribute to the aroma, color, and flavor characters of wine. The pericarp, which is composed of the exocarp (skin) and mesocarp (pulp), not only functions to protect and feed the developing seed, but also to assist in the dispersal of the mature seed by avian and mammalian vectors. The skin provides volatile and nonvolatile aroma and color compounds, the pulp contributes organic acids and sugars, and the seeds provide condensed tannins, all of which are important to the formation of organoleptic characteristics of wine. In order to understand the transcriptional network responsible for controlling tissue-specific mRNA expression patterns, mRNA expression profiling was conducted on each tissue of mature berries of V. vinifera Cabernet Sauvignon using the Affymetrix GeneChip(R) Vitis oligonucleotide microarray ver. 1.0. In order to monitor the influence of water-deficit stress on tissue-specific expression patterns, mRNA expression profiles were also compared from mature berries harvested from vines subjected to well-watered or water-deficit conditions.ResultsOverall, berry tissues were found to express approximately 76% of genes represented on the Vitis microarray. Approximately 60% of these genes exhibited significant differential expression in one or more of the three major tissue types with more than 28% of genes showing pronounced (2-fold or greater) differences in mRNA expression. The largest difference in tissue-specific expression was observed between the seed and pulp/skin. Exocarp tissue, which is involved in pathogen defense and pigment production, showed higher mRNA abundance relative to other berry tissues for genes involved with flavonoid biosynthesis, pathogen resistance, and cell wall modification. Mesocarp tissue, which is considered a nutritive tissue, exhibited a higher mRNA abundance of genes involved in cell wall function and transport processes. Seeds, which supply essential resources for embryo development, showed higher mRNA abundance of genes encoding phenylpropanoid biosynthetic enzymes, seed storage proteins, and late embryogenesis abundant proteins. Water-deficit stress affected the mRNA abundance of 13% of the genes with differential expression patterns occurring mainly in the pulp and skin. In pulp and seed tissues transcript abundance in most functional categories declined in water-deficit stressed vines relative to well-watered vines with transcripts for storage proteins and novel (no-hit) functional assignments being over represented. In the skin of berries from water-deficit stressed vines, however, transcripts from several functional categories including general phenypropanoid and ethylene metabolism, pathogenesis-related responses, energy, and interaction with the environment were significantly over-represented.ConclusionThese results revealed novel insights into the tissue-specific expression mRNA expression patterns of an extensive repertoire of genes expressed in berry tissues. This work also establishes an extensive catalogue of gene expression patterns for future investigations aimed at the dissection of the transcriptional regulatory hierarchies that govern tissue-specific expression patterns associated with tissue differentiation within berries. These results also confirmed that water-deficit stress has a profound effect on mRNA expression patterns particularly associated with the biosynthesis of aroma and color metabolites within skin and pulp tissues that ultimately impact wine quality.

Project description:BackgroundThe pathogenesis of human immunodeficiency virus 1 (HIV-1) infection is so complex that have not been clearly defined, despite intensive efforts have been made by many researchers. MicroRNA (miRNA) as regulation factor in various human diseases may influence the course of HIV-1 infection by targeting mRNAs. Thus, studies combining transcription of posttranscriptional miRNA regulation are required.MethodsWith the purpose of identifying cascaded miRNA-mRNA regulatory relationships related to HIV infection in gene level, the parallel miRNA, and mRNA expression profiles were analyzed to select differential expressed miRNAs and mRNAs. Then, miRNA-mRNA interactions were predicted using 3 data sources and Pearson correlation coefficient was calculated based on the gene expression level for accuracy improvement. Furthermore, the calculation of the regulatory impact factors was conducted to reveal crucial regulators in HIV-1 infection. To give further insight into these transcription factor (TF) regulators, the differentially co-expression analysis was conducted to identify differentially co-expressed links and differential co-expressed genes and the co-expression gene modules were identified using a threshold-based hierarchical clustering method, then modules were combined into a miRNA-TF-mRNA network.ResultsA total of 69,126 differentially co-expressed links and 626 differential co-expressed genes were identified. Functional enrichment analysis indicated that these co-expressed genes were significantly involved in immune response and apoptosis. Moreover, according to regulatory impact factors, 5 most influential TFs and miRNA in HIV-1 infection were identified and miRNA-TF-mRNA regulatory networks were built during the computing process.ConclusionsIn our study, a set of integrated methods was generated to identify important regulators and miRNA-TF-mRNA interactions. Parallel profiling analysis of the miRNAs and mRNAs expression of HIV/acquired immunodeficiency syndrome (AIDS) patients after antiretroviral therapy indicated that some regulators have wide impact on gene regulation and that these regulatory elements may bear significant implications on the underlying molecular mechanism and pathogenesis of AIDS occurrence.

Dataset Information

Tissue and process specific microRNA-mRNA co-expression in mammalian development and malignancy.

Publications

Tissue and process specific microRNA-mRNA co-expression in mammalian development and malignancy.

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