MicroRNAs and their isomiRs function cooperatively to target common biological pathways
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE29101 | GEO | 2011/12/21
SECONDARY ACCESSION(S): PRJNA140357
REPOSITORIES: GEO
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Project description:BACKGROUND:Variants of microRNAs (miRNAs), called isomiRs, are commonly reported in deep-sequencing studies; however, the functional significance of these variants remains controversial. Observational studies show that isomiR patterns are non-random, hinting that these molecules could be regulated and therefore functional, although no conclusive biological role has been demonstrated for these molecules. RESULTS:To assess the biological relevance of isomiRs, we have performed ultra-deep miRNA-seq on ten adult human tissues, and created an analysis pipeline called miRNA-MATE to align, annotate, and analyze miRNAs and their isomiRs. We find that isomiRs share sequence and expression characteristics with canonical miRNAs, and are generally strongly correlated with canonical miRNA expression. A large proportion of isomiRs potentially derive from AGO2 cleavage independent of Dicer. We isolated polyribosome-associated mRNA, captured the mRNA-bound miRNAs, and found that isomiRs and canonical miRNAs are equally associated with translational machinery. Finally, we transfected cells with biotinylated RNA duplexes encoding isomiRs or their canonical counterparts and directly assayed their mRNA targets. These studies allow us to experimentally determine genome-wide mRNA targets, and these experiments showed substantial overlap in functional mRNA networks suppressed by both canonical miRNAs and their isomiRs. CONCLUSIONS:Together, these results find isomiRs to be biologically relevant and functionally cooperative partners of canonical miRNAs that act coordinately to target pathways of functionally related genes. This work exposes the complexity of the miRNA-transcriptome, and helps explain a major miRNA paradox: how specific regulation of biological processes can occur when the specificity of miRNA targeting is mediated by only 6 to 11 nucleotides.
| S-EPMC3334621 | biostudies-literature
Project description:This SuperSeries is composed of the following subset Series: GSE29043: MicroRNAs and their isomiRs function cooperatively to target common biological pathways (Illumina expression beadchip) GSE29100: MicroRNAs and their isomiRs function cooperatively to target common biological pathways (Agilent miRNA array) Refer to individual Series This represents the miRNA placenta samples and mRNA + miRNA pulldown only The miRNA-Seq data have been submitted to the short read archive under SRA number SRP006043: http://www.ncbi.nlm.nih.gov/sra?term= SRP006043
2011-12-21 | E-GEOD-29101 | biostudies-arrayexpress
Project description:Variants of microRNAs, (isomiRs) are commonly reported in deep-sequencing studies; however the functional significance of these variants remains controversial. To assess their biological relevance, we have performed ultra-deep miRNA-seq on ten adult human tissues, and created an analysis pipeline (miRNA-MATE) to align, annotate, and analyze miRNAs and their isomiRs. We find that isomiRs share sequence and expression characteristics with canonical miRNAs, and are generally strongly correlated with canonical miRNA expression. We isolated polyribosome-associated mRNA, and captured the mRNA-bound miRNAs, and found that isomiRs and canonical miRNAs are equally associated with translational machinery. Finally, we transfected cells with biotinylated RNA duplexes encoding isomiRs or their canonical counterparts and directly assayed their mRNA targets. These studies showed substantial overlap in functional mRNA networks suppressed by both canonical miRNAs and their isomiRs. Together, these results find isomiRs to be biologically relevant and functionally synergistic partners of canonical miRNAs that act coordinately to target pathways of functionally related genes. This work exposes the complexity of the miRNA-transcriptome, and helps explain a major miRNA paradox: how specific regulation of biological processes can occur with predominantly non-specific miRNA-mRNA interactions. HEK293T cells were transfected with biotinylated miRNAs (either mir-10a-iso, mir-10a, mir-10b-iso or mir-10b) or a mock control. The miRNAs and target mRNA were pulled down with streptavidin. The pulled down RNA was hybridised to Illumina microarrays. The miRNA-Seq data have been submitted to the short read archive under SRA number SRP006043: http://www.ncbi.nlm.nih.gov/sra?term= SRP006043
2011-12-21 | E-GEOD-29043 | biostudies-arrayexpress
Project description:This data set is part of a larger study: Variants of microRNAs, (isomiRs) are commonly reported in deep-sequencing studies; however the functional significance of these variants remains controversial. To assess their biological relevance, we have performed ultra-deep miRNA-seq on ten adult human tissues, and created an analysis pipeline (miRNA-MATE) to align, annotate, and analyze miRNAs and their isomiRs. We find that isomiRs share sequence and expression characteristics with canonical miRNAs, and are generally strongly correlated with canonical miRNA expression. We isolated polyribosome-associated mRNA, and captured the mRNA-bound miRNAs, and found that isomiRs and canonical miRNAs are equally associated with translational machinery. Finally, we transfected cells with biotinylated RNA duplexes encoding isomiRs or their canonical counterparts and directly assayed their mRNA targets. These studies showed substantial overlap in functional mRNA networks suppressed by both canonical miRNAs and their isomiRs. Together, these results find isomiRs to be biologically relevant and functionally synergistic partners of canonical miRNAs that act coordinately to target pathways of functionally related genes. This work exposes the complexity of the miRNA-transcriptome, and helps explain a major miRNA paradox: how specific regulation of biological processes can occur with predominantly non-specific miRNA-mRNA interactions. 6 samples submitted, all replicates of Human Placenta total RNA, Ambion The miRNA-Seq data have been submitted to the short read archive under SRA number SRP006043: http://www.ncbi.nlm.nih.gov/sra?term= SRP006043
2011-12-21 | E-GEOD-29100 | biostudies-arrayexpress
Project description:This data set is part of a larger study: Variants of microRNAs, (isomiRs) are commonly reported in deep-sequencing studies; however the functional significance of these variants remains controversial. To assess their biological relevance, we have performed ultra-deep miRNA-seq on ten adult human tissues, and created an analysis pipeline (miRNA-MATE) to align, annotate, and analyze miRNAs and their isomiRs. We find that isomiRs share sequence and expression characteristics with canonical miRNAs, and are generally strongly correlated with canonical miRNA expression. We isolated polyribosome-associated mRNA, and captured the mRNA-bound miRNAs, and found that isomiRs and canonical miRNAs are equally associated with translational machinery. Finally, we transfected cells with biotinylated RNA duplexes encoding isomiRs or their canonical counterparts and directly assayed their mRNA targets. These studies showed substantial overlap in functional mRNA networks suppressed by both canonical miRNAs and their isomiRs. Together, these results find isomiRs to be biologically relevant and functionally synergistic partners of canonical miRNAs that act coordinately to target pathways of functionally related genes. This work exposes the complexity of the miRNA-transcriptome, and helps explain a major miRNA paradox: how specific regulation of biological processes can occur with predominantly non-specific miRNA-mRNA interactions.
2011-12-21 | GSE29100 | GEO
Project description:Variants of microRNAs, (isomiRs) are commonly reported in deep-sequencing studies; however the functional significance of these variants remains controversial. To assess their biological relevance, we have performed ultra-deep miRNA-seq on ten adult human tissues, and created an analysis pipeline (miRNA-MATE) to align, annotate, and analyze miRNAs and their isomiRs. We find that isomiRs share sequence and expression characteristics with canonical miRNAs, and are generally strongly correlated with canonical miRNA expression. We isolated polyribosome-associated mRNA, and captured the mRNA-bound miRNAs, and found that isomiRs and canonical miRNAs are equally associated with translational machinery. Finally, we transfected cells with biotinylated RNA duplexes encoding isomiRs or their canonical counterparts and directly assayed their mRNA targets. These studies showed substantial overlap in functional mRNA networks suppressed by both canonical miRNAs and their isomiRs. Together, these results find isomiRs to be biologically relevant and functionally synergistic partners of canonical miRNAs that act coordinately to target pathways of functionally related genes. This work exposes the complexity of the miRNA-transcriptome, and helps explain a major miRNA paradox: how specific regulation of biological processes can occur with predominantly non-specific miRNA-mRNA interactions.
2011-12-21 | GSE29043 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
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Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
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Project description:Polymorphisms in microRNAs (miRNAs) and their target sites (PolymiRTS) are known to disrupt miRNA function, leading to the development of disease and variation in physiological and behavioral phenotypes. Here, we describe recent updates to the PolymiRTS database (http://compbio.uthsc.edu/miRSNP), an integrated platform for analyzing the functional impact of genetic polymorphisms in miRNA seed regions and miRNA target sites. Recent advances in genomic technologies have made it possible to identify miRNA-mRNA binding sites from direct mapping experiments such as CLASH (cross linking, ligation and sequencing of hybrids). We have integrated data from CLASH experiments in the PolymiRTS database to provide more complete and accurate miRNA-mRNA interactions. Other significant new features include (i) small insertions and deletions in miRNA seed regions and miRNA target sites, (ii) TargetScan context + score differences for assessing the impact of polymorphic miRNA-mRNA interactions and (iii) biological pathways. The browse and search pages of PolymiRTS allow users to explore the relations between the PolymiRTSs and gene expression traits, physiological and behavioral phenotypes, human diseases and biological pathways.
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Project description:This SuperSeries is composed of the SubSeries listed below.
2013-12-30 | GSE41372 | GEO